Difference between revisions of "Staging page"

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[[#top|Back to Top]]
 
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</div>
 
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{{#lst:Section editor transclusions|anhl}}
 
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''Are you looking for a regimen, such as [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]], but can't find it here? It is possible that we've moved it to the [[Diffuse_large_B-cell_lymphoma_-_historical|historical regimens page]]. For placebo or observational studies in this condition, please visit [[Diffuse_large_B-cell_lymphoma_-_null_regimens|this page]]. If you still can't find it, please let us know so we can add it!''
 
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For pediatric regimens, please visit the [[Non-Hodgkin lymphoma, pediatric|pediatric NHL page]].
 
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{| class="wikitable" style="float:right; margin-right: 5px;"
 
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|-
 
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|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
 
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<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 
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|}
 
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{{TOC limit|limit=3}}
 
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=Guidelines=
 
−
==BSH==
 
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*'''2020:''' McKay et al. [https://doi.org/full/10.1111/bjh.16866 The prevention of central nervous system relapse in diffuse large B-cell lymphoma: a British Society for Haematology good practice paper]
 
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==[http://www.esmo.org/ ESMO]==
 
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*'''2015:''' Tilly et al. [https://www.esmo.org/Guidelines/Haematological-Malignancies/Diffuse-Large-B-Cell-Lymphoma Diffuse large B-cell lymphoma (DLBCL): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
 
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===Older===
 
−
*'''2013:''' Ghielmini et al. [http://annonc.oxfordjournals.org/content/24/3/561.full.pdf+html ESMO Guidelines consensus conference on malignant lymphoma 2011 part 1: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL)] [https://pubmed.ncbi.nlm.nih.gov/23175624 PubMed]
 
−
==[https://www.nccn.org/ NCCN]==
 
−
*[https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf NCCN Guidelines - B-cell Lymphomas]
 
−
*[https://www.nccn.org/professionals/physician_gls/pdf/ped_b-cell.pdf NCCN Guidelines - Pediatric Aggressive Mature B-Cell Lymphomas]
 
−
==SITC==
 
−
*'''2020:''' Neelapu et al. [https://doi.org/10.1136%2Fjitc-2020-001235 Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of lymphoma]
 
−
=Untreated, pre-phase=
 
−
==Vincristine & Prednisone {{#subobject:3f87a0|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, PO vincristine {{#subobject:561457|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/S2352-3026(16)30171-5 Peyrade et al. 2016 (LYSA LNH09-7B)]
 
−
|2010-2011
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Vincristine (Oncovin)]] 1 mg PO once on day -7
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 60 mg PO once per day on days -7 to -4
 
−
'''7-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#O-miniCHOP|O-miniCHOP]]
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, IV vincristine {{#subobject:722d93|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/104/3/626.long Pfreundschuh et al. 2004 (NHL-B1)]
 
−
|1993-2000
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|[http://www.bloodjournal.org/content/104/3/634.long Pfreundschuh et al. 2004 (NHL-B2)]
 
−
|1993-2000
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045%2808%2970002-0 Pfreundschuh et al. 2008 (RICOVER-60)]
 
−
|2000-2005
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2013.54.6861 Pfreundschuh et al. 2014 (SMARTE-R-CHOP-14)]
 
−
|2007-2009
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Note: This was recommended in NHL-B1 and NHL-B2 "to improve the performance status of patients and to ameliorate side-effects of the first chemotherapy cycle." Mandated in RICOVER-60 and SMARTE-R-CHOP-14. NHL-B1 gave the option of a 5 to 7 day course of prednisone.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Vincristine (Oncovin)]] 1 mg IV once (day not specified)
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 7
 
−
'''7-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*NHL-B1 and NHL-B2: [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]] versus [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP-14|CHOP-14]] versus [[Diffuse_large_B-cell_lymphoma_-_historical#CHOEP-14|CHOEP-14]] versus [[Diffuse_large_B-cell_lymphoma_-_historical#CHOEP-21|CHOEP-21]]
 
−
*RICOVER-60: [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP-14|CHOP-14]] versus [[#R-CHOP-14|R-CHOP-14]]
 
−
*SMARTE-R-CHOP-14: [[#R-CHOP-14|R-CHOP-14]]
 
−
</div></div>
 
−
===References===
 
−
#'''NHL-B1:''' Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rudolph C, Reiser M, Hossfeld DK, Metzner B, Hasenclever D, Schmitz N, Glass B, Rübe C, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):626-33. Epub 2004 Feb 24. [http://www.bloodjournal.org/content/104/3/626.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14982884 PubMed]
 
−
#'''NHL-B2:''' Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rübe C, Rudolph C, Reiser M, Hossfeld DK, Eimermacher H, Hasenclever D, Schmitz N, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):634-41. Epub 2004 Mar 11. [http://www.bloodjournal.org/content/104/3/634.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15016643 PubMed]
 
−
#'''RICOVER-60:''' Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, Reiser M, Nickenig C, Clemens M, Peter N, Bokemeyer C, Eimermacher H, Ho A, Hoffmann M, Mertelsmann R, Trümper L, Balleisen L, Liersch R, Metzner B, Hartmann F, Glass B, Poeschel V, Schmitz N, Ruebe C, Feller AC, Loeffler M; German High-Grade Non-Hodgkin Lymphoma Study Group. Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol. 2008 Feb;9(2):105-16. [https://doi.org/10.1016/S1470-2045%2808%2970002-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18226581 PubMed] NCT00052936
 
−
#'''SMARTE-R-CHOP-14:''' Pfreundschuh M, Poeschel V, Zeynalova S, Hänel M, Held G, Schmitz N, Viardot A, Dreyling MH, Hallek M, Mueller C, Wiesen MH, Witzens-Harig M, Truemper L, Keller U, Rixecker T, Zwick C, Murawski N; German High-Grade Non-Hodgkin Lymphoma Study Group. Optimization of rituximab for the treatment of diffuse large B-cell lymphoma (II): extended rituximab exposure time in the SMARTE-R-CHOP-14 trial of the German High-Grade Non-Hodgkin Lymphoma Study Group. J Clin Oncol. 2014 Dec 20;32(36):4127-33. Epub 2014 Nov 17. Erratum in: J Clin Oncol. 2015 Jun 10;33(17):1991. [https://doi.org/10.1200/jco.2013.54.6861 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25403207 PubMed] NCT00052936
 
−
#'''LYSA LNH09-7B:''' Peyrade F, Bologna S, Delwail V, Emile JF, Pascal L, Fermé C, Schiano JM, Coiffier B, Corront B, Farhat H, Fruchart C, Ghesquieres H, Macro M, Tilly H, Choufi B, Delarue R, Fitoussi O, Gabarre J, Haioun C, Jardin F. Combination of ofatumumab and reduced-dose CHOP for diffuse large B-cell lymphomas in patients aged 80 years or older: an open-label, multicentre, single-arm, phase 2 trial from the LYSA group. Lancet Haematol. 2017 Jan;4(1):e46-e55. [https://doi.org/10.1016/S2352-3026(16)30171-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28041583 PubMed] NCT01195714
 
−
=Untreated, randomized data=
 
−
==Pola-R-CHP {{#subobject:ugj1b2|Regimen=1}}==
 
−
Pola-R-CHP: '''<u>Pola</u>'''tuzumab, '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:e3jh13|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa2115304 Tilly et al. 2021 (POLARIX)]
 
−
|2017-2019
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 
−
|[[#R-CHOP|R-CHOP]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>PFS24: 76.7% vs 70.2%<br>(HR 0.73, 95% CI 0.57-0.95)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Antibody-drug conjugate therapy====
 
−
*[[Polatuzumab vedotin (Polivy)]] as follows:
 
−
**Cycles 1 to 6: 1.8 mg/kg IV once on day 1
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 1 to 6: 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] as follows:
 
−
**Cycles 1 to 6: 50 mg/m<sup>2</sup> IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] as follows:
 
−
**Cycles 1 to 6: 100 mg PO once per day on days 1 to 5
 
−
'''21-day cycle for 8 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''POLARIX:''' Tilly H, Morschhauser F, Sehn LH, Friedberg JW, Trněný M, Sharman JP, Herbaux C, Burke JM, Matasar M, Rai S, Izutsu K, Mehta-Shah N, Oberic L, Chauchet A, Jurczak W, Song Y, Greil R, Mykhalska L, Bergua-Burgués JM, Cheung MC, Pinto A, Shin HJ, Hapgood G, Munhoz E, Abrisqueta P, Gau JP, Hirata J, Jiang Y, Yan M, Lee C, Flowers CR, Salles G. Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. N Engl J Med. 2022 Jan 27;386(4):351-363. Epub 2021 Dec 14. [https://doi.org/10.1056/nejmoa2115304 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34904799/ PubMed] NCT03274492
 
−
==R-ACVBP {{#subobject:bb17b2|Regimen=1}}==
 
−
R-ACVBP: '''<u>R</u>'''ituximab, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''indesine, '''<u>B</u>'''leomycin, '''<u>P</u>'''rednisone
 
−
<br>ACVBP-R: '''<u>A</u>'''driamycin (Doxorubicin), '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''indesine, '''<u>B</u>'''leomycin, '''<u>P</u>'''rednisone, '''<u>R</u>'''ituximab
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:1cd335|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(11)61040-4 Récher et al. 2011 (LNH03-2B)]
 
−
|2003-2008
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#R-CHOP|R-CHOP]]
 
−
| style="background-color:#1a9850" |Superior OS<br>OS36: 92% vs 84%<br>(HR 0.44, 95% CI 0.28-0.81)
 
−
| style="background-color:#d73027" |Increased toxicity
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mds600 Ketterer et al. 2013 (LNH03-1B)]
 
−
|2003-2008
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Diffuse_large_B-cell_lymphoma_-_historical#ACVBP|ACVBP]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>PFS36: 95% vs 83%<br>(HR 0.37, 95% CI 0.15-0.89)
 
−
| style="background-color:#eeee01" |Similar toxicity
 
−
|-
 
−
|[https://doi.org/10.1182/blood.2020008750 Le Gouill et al. 2021 (GAINED)]
 
−
|2012-2015
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#G-ACVBP_99|G-ACVBP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS<br>EFS24: 57% vs 60%<br>(HR 1.14, 95% CI 0.91-1.43)
 
−
|
 
−
|-
 
−
|}
 
−
''Note: Treatment in GAINED was PET-adapted; see paper for details.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Doxorubicin (Adriamycin)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vindesine (Eldisine)]] 2 mg/m<sup>2</sup> IV once per day on days 1 & 5
 
−
*[[Bleomycin (Blenoxane)]] 10 units IV once per day on days 1 & 5
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] 15 mg IT on day 1
 
−
====Supportive therapy====
 
−
*[[Filgrastim (Neupogen)]] 300 mcg (for patients less than 75 kg) or 480 mcg (for patients greater than or equal to 75 kg) SC once per day on days 6 to 13
 
−
'''14-day cycle for 4 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#Methotrexate_monotherapy|Methotrexate]] consolidation, in 4 weeks
 
−
</div></div>
 
−
===References===
 
−
#'''LNH03-2B:''' Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O, Thiéblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquières H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais JP, Salles G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011 Nov 26;378(9806):1858-67. [https://doi.org/10.1016/S0140-6736(11)61040-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22118442 PubMed] NCT00140595
 
−
##'''Subgroup analysis:''' Molina TJ, Canioni D, Copie-Bergman C, Recher C, Brière J, Haioun C, Berger F, Fermé C, Copin MC, Casasnovas O, Thieblemont C, Petrella T, Leroy K, Salles G, Fabiani B, Morschauser F, Mounier N, Coiffier B, Jardin F, Gaulard P, Jais JP, Tilly H. Young patients with non-germinal center B-cell-like diffuse large B-cell lymphoma benefit from intensified chemotherapy with ACVBP plus rituximab compared with CHOP plus rituximab: analysis of data from the Groupe d'Etudes des Lymphomes de l'Adulte/lymphoma study association phase III trial LNH 03-2B. J Clin Oncol. 2014 Dec 10;32(35):3996-4003. Epub 2014 Nov 10. [https://doi.org/10.1200/JCO.2013.54.9493 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25385729 PubMed]
 
−
#'''LNH03-1B:''' Ketterer N, Coiffier B, Thieblemont C, Fermé C, Brière J, Casasnovas O, Bologna S, Christian B, Connerotte T, Récher C, Bordessoule D, Fruchart C, Delarue R, Bonnet C, Morschhauser F, Anglaret B, Soussain C, Fabiani B, Tilly H, Haioun C. Phase III study of ACVBP versus ACVBP plus rituximab for patients with localized low-risk diffuse large B-cell lymphoma (LNH03-1B). Ann Oncol. 2013 Apr;24(4):1032-7. Epub 2012 Dec 12. [https://doi.org/10.1093/annonc/mds600 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23235801 PubMed] NCT00140595
 
−
#'''GAINED:''' Le Gouill S, Ghesquières H, Oberic L, Morschhauser F, Tilly H, Ribrag V, Lamy T, Thieblemont C, Maisonneuve H, Gressin R, Bouhabdallah K, Haioun C, Damaj G, Fornecker L, Bouhabdallah R, Feugier P, Sibon D, Cartron G, Bonnet C, André M, Chartier L, Ruminy P, Kraeber-Bodéré F, Bodet-Milin C, Berriolo-Riedinger A, Brière J, Jais JP, Molina TJ, Itti E, Casasnovas RO. Obinutuzumab vs rituximab for advanced DLBCL: a PET-guided and randomized phase 3 study by LYSA. Blood. 2021 Apr 29;137(17):2307-2320. [https://doi.org/10.1182/blood.2020008750 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/33211799/ PubMed] NCT01659099
 
−
==R-CEOP70 {{#subobject:1ygjg1|Regimen=1}}==
 
−
R-CEOP70: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''pirubicin ('''<u>70</u>''' mg/m<sup>2</sup> dosing), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:u1xx91|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1016/s2352-3026(19)30051-1 Xu et al. 2019 (NHL-001)]
 
−
|rowspan=2|2013-2016
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|1. [[#R-CEOP90|R-CEOP90]]
 
−
| style="background-color:#d73027" |Inferior PFS24
 
−
|-
 
−
|2. [[#R-CHOP|R-CHOP]]
 
−
| style="background-color:#eeee01" |Non-inferior PFS24<br>PFS24: 72.4% vs 72.5%<br>(HR 1.00, 95% CI 0.72-1.37)
 
−
|-
 
−
|}
 
−
''Note: this arm was available to patients of all ages.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 0
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 1 to 6: 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] as follows:
 
−
**Cycles 1 to 6: 70 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] as follows:
 
−
**Cycles 1 to 6: 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisolone (Millipred)]] as follows:
 
−
**Cycles 1 to 6: 60 mg/m<sup>2</sup>/day (maximum dose of 100 mg) PO on days 1 to 5
 
−
'''21-day cycle for 8 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients with bulky disease at diagnosis or residual masses at end of treatment: [[#Radiation_therapy|IFRT]]
 
−
</div></div>
 
−
===References===
 
−
#'''NHL-001:''' Xu PP, Fu D, Li JY, Hu JD, Wang X, Zhou JF, Yu H, Zhao X, Huang YH, Jiang L, Liu F, Su LP, Chen ZW, Zeng QS, Chen JP, Fang MY, Ma J, Liu T, Song YP, Yu K, Li Y, Qiu LG, Chen XQ, Gu J, Yan JS, Hou M, Huang HY, Wang L, Cheng S, Shen Y, Xiong H, Chen SJ, Zhao WL. Anthracycline dose optimisation in patients with diffuse large B-cell lymphoma: a multicentre, phase 3, randomised, controlled trial. Lancet Haematol. 2019 Jun;6(6):e328-e337. [https://doi.org/10.1016/s2352-3026(19)30051-1 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/31126528/ PubMed] NCT01852435
 
−
==R-CEOP90 {{#subobject:1ygd7e|Regimen=1}}==
 
−
R-CEOP90: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''pirubicin ('''<u>90</u>''' mg/m<sup>2</sup> dosing), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:d1ug91|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1016/s2352-3026(19)30051-1 Xu et al. 2019 (NHL-001)]
 
−
|rowspan=2|2013-2016
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#R-CEOP70|R-CEOP70]]
 
−
| style="background-color:#1a9850" |Superior PFS24<br>PFS24: 89% vs 77%<br>(HR 0.49, 95% CI 0.27-0.86)
 
−
|-
 
−
|2. [[#R-CHOP|R-CHOP]]
 
−
| style="background-color:#1a9850" |Superior PFS24<br>PFS24: 89% vs 76%<br>(HR 0.44, 95% CI 0.25-0.76)
 
−
|-
 
−
|}
 
−
''Note: this arm was only available to patients aged 16-60 years.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 0
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 1 to 6: 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] as follows:
 
−
**Cycles 1 to 6: 90 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] as follows:
 
−
**Cycles 1 to 6: 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisolone (Millipred)]] as follows:
 
−
**Cycles 1 to 6: 60 mg/m<sup>2</sup>/day (maximum dose of 100 mg) PO on days 1 to 5
 
−
'''21-day cycle for 8 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients with bulky disease at diagnosis or residual masses at end of treatment: [[#Radiation_therapy|IFRT]]
 
−
</div></div>
 
−
===References===
 
−
#'''NHL-001:''' Xu PP, Fu D, Li JY, Hu JD, Wang X, Zhou JF, Yu H, Zhao X, Huang YH, Jiang L, Liu F, Su LP, Chen ZW, Zeng QS, Chen JP, Fang MY, Ma J, Liu T, Song YP, Yu K, Li Y, Qiu LG, Chen XQ, Gu J, Yan JS, Hou M, Huang HY, Wang L, Cheng S, Shen Y, Xiong H, Chen SJ, Zhao WL. Anthracycline dose optimisation in patients with diffuse large B-cell lymphoma: a multicentre, phase 3, randomised, controlled trial. Lancet Haematol. 2019 Jun;6(6):e328-e337. [https://doi.org/10.1016/s2352-3026(19)30051-1 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/31126528/ PubMed] NCT01852435
 
−
==R-CHOEP-14 {{#subobject:75c24e|Regimen=1}}==
 
−
R-CHOEP-14: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>14</u>'''-day cycles
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, flat-dose vincristine {{#subobject:b156e5|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://link.springer.com/article/10.1385%2FMO%3A23%3A2%3A283 Adde et al. 2006]
 
−
|2001-2003
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(12)70481-3 Schmitz et al. 2012 (DSHNHL 2002-1)]
 
−
|2003-2009
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Stub#R-MegaCHOEP|R-MegaCHOEP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 
−
| style="background-color:#1a9851" |Decreased toxicity
 
−
|-
 
−
|}
 
−
''Note: to our knowledge, this regimen was not tested as an experimental arm in a RCT prior to becoming a standard comparator arm.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycles 1 to 4, 6, 8: 375 mg/m<sup>2</sup> IV once on day 0
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
'''14-day cycle for 8 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*"Mandatory" for patients with bulky disease (any mass greater than 7.5cm in diameter, or extranodal involvement): [[#Radiation_therapy|RT]] x 36 Gy
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, capped vincristine, with CNS prophylaxis {{#subobject:0258f4|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mds621 Holte et al. 2012 (NLG LBC-04)]
 
−
|2004-2008
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Note: Consolidative radiotherapy "given at the discretion of the individual centers (36 to 45 Gy). Indications for giving radiotherapy after the completion of chemotherapy included bulky disease (greater than or equal to 10 cm) at diagnosis, localized PET-positive residual lesions, and residual disease, not eligible for biopsy at a localized site, and potentially curable by radiotherapy."''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
====Supportive therapy====
 
−
*ONE of the following:
 
−
**[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day from day 4
 
−
**[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 4
 
−
'''14-day cycle for 8 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*CNS prophylaxis: [[CNS_lymphoma#Cytarabine_monotherapy|HiDAC]], then [[CNS_lymphoma#Methotrexate_monotherapy|HD-MTX]]
 
−
</div></div>
 
−
===References===
 
−
#Adde M, Enblad G, Hagberg H, Sundström C, Laurell A. Outcome for young high-risk aggressive B-cell lymphoma patients treated with CHOEP-14 and rituximab (R-CHOEP-14). Med Oncol. 2006;23(2):283-93. [https://link.springer.com/article/10.1385%2FMO%3A23%3A2%3A283 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16720929 PubMed]
 
−
#'''DSHNHL 2002-1:''' Schmitz N, Nickelsen M, Ziepert M, Haenel M, Borchmann P, Schmidt C, Viardot A, Bentz M, Peter N, Ehninger G, Doelken G, Ruebe C, Truemper L, Rosenwald A, Pfreundschuh M, Loeffler M, Glass B; German High-Grade Lymphoma Study Group. Conventional chemotherapy (CHOEP-14) with rituximab or high-dose chemotherapy (MegaCHOEP) with rituximab for young, high-risk patients with aggressive B-cell lymphoma: an open-label, randomised, phase 3 trial (DSHNHL 2002-1). Lancet Oncol. 2012 Dec;13(12):1250-1259. Epub 2012 Nov 16. [https://doi.org/10.1016/S1470-2045(12)70481-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23168367 PubMed] NCT00129090
 
−
##'''Update:''' Frontzek F, Ziepert M, Nickelsen M, Altmann B, Glass B, Haenel M, Truemper L, Held G, Bentz M, Borchmann P, Dreyling M, Viardot A, Kroschinsky FP, Metzner B, Staiger AM, Horn H, Ott G, Rosenwald A, Loeffler M, Lenz G, Schmitz N. Rituximab plus high-dose chemotherapy (MegaCHOEP) or conventional chemotherapy (CHOEP-14) in young, high-risk patients with aggressive B-cell lymphoma: 10-year follow-up of a randomised, open-label, phase 3 trial. Lancet Haematol. 2021 Apr;8(4):e267-e277. Epub 2021 Mar 2. [https://doi.org/10.1016/s2352-3026(21)00022-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33667420/ PubMed]
 
−
#'''NLG LBC-04:''' Holte H, Leppä S, Björkholm M, Fluge O, Jyrkkiö S, Delabie J, Sundström C, Karjalainen-Lindsberg ML, Erlanson M, Kolstad A, Fosså A, Ostenstad B, Löfvenberg E, Nordström M, Janes R, Pedersen LM, Anderson H, Jerkeman M, Eriksson M. Dose-densified chemoimmunotherapy followed by systemic central nervous system prophylaxis for younger high-risk diffuse large B-cell/follicular grade 3 lymphoma patients: results of a phase II Nordic Lymphoma Group study. Ann Oncol. 2013 May;24(5):1385-92. Epub 2012 Dec 17. [https://doi.org/10.1093/annonc/mds621 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23247661 PubMed] NCT01502982
 
−
==R-CHOP {{#subobject:240cc2|Regimen=1}}==
 
−
R-CHOP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone
 
−
<br>R-CHOP-21: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone given every '''<u>21</u>''' days
 
−
<br>CHOP-R: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone, '''<u>R</u>'''ituximab
 
−
<br>RCHOP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone
 
−
<br>CHOPR: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone, '''<u>R</u>'''ituximab
 
−
===Example orders===
 
−
*[[Example orders for R-CHOP in lymphoma]]
 
−
''Note: most of the variation between regimen variants is in the dose of prednisone.''
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, prednisone 40 mg/m<sup>2</sup> {{#subobject:a326e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa011795 Coiffier et al. 2002 (LNH 98-5)]
 
−
|1998-2000
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]]
 
−
| style="background-color:#1a9850" |Superior OS<br>OS24: 70% vs 57%<br>(HR 0.64, 95% CI 0.45-0.89)
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(13)70122-0 Delarue et al. 2013 (LNH03-6B)]
 
−
|2003-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#R-CHOP-14|R-CHOP-14]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
====Supportive therapy====
 
−
*[[Filgrastim (Neupogen)]] used for later cycles if patients developed grade 4 neutropenia or febrile neutropenia
 
−
'''21-day cycle for 8 cycles'''
 
−
====CNS therapy, prophylaxis====
 
−
As described in Delarue et al. 2013 (LNH03-6B):
 
−
*[[Methotrexate (MTX)]] 15 mg IT once on day 1
 
−
'''21-day cycle for 4 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, prednisone 60 mg/m<sup>2</sup> {{#subobject:18b582|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(11)61040-4 Récher et al. 2011 (LNH03-2B)]
 
−
|2003-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#R-ACVBP|R-ACVBP]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
| style="background-color:#1a9851" |Decreased toxicity
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639223/ Li et al. 2018 (CSWOG0001)]
 
−
|2008-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#R-CHOP-14|R-CHOP-14]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
| style="background-color:#ffffbf" |Similar toxicities
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
'''21-day cycle for 8 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, prednisone 100 mg, capped vincristine, 4 cycles {{#subobject:13e2ib|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(19)33008-9 Poeschel et al. 2019 (FLYER)]
 
−
|2005-2016
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|[[#R-CHOP|R-CHOP]] x 6
 
−
| style="background-color:#eeee01" |Non-inferior PFS<br>PFS36: 96% vs 93%
 
−
| style="background-color:#1a9850" |Less toxic
 
−
|-
 
−
|}
 
−
''Note: Patients in FLYER were 18 to 60 and had no risk factors according to age-adjusted IPI.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 1 to 4: 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] as follows:
 
−
**Cycles 1 to 4: 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] as follows:
 
−
**Cycles 1 to 4: 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] as follows:
 
−
**Cycles 1 to 4: 100 mg IV or PO once per day on days 1 to 5
 
−
'''21-day cycle for 4 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #4, prednisone 100 mg, capped vincristine, 6 cycles {{#subobject:13e254|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2001.19.2.389 Vose et al. 2001]
 
−
|NR
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.3109/10428194.2011.621565 Merli et al. 2012 (ANZINTER3)]
 
−
|2003-2006
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#R-miniCEOP|R-miniCEOP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdt289 Herbrecht et al. 2013 (PIX203)]
 
−
|2005-2008
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 
−
|[[#CPOP-R_99|CPOP-R]]
 
−
| style="background-color:#ffffbf" |Inconclusive whether non-inferior CR/CRu rate<sup>1</sup>
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(19)33008-9 Poeschel et al. 2019 (FLYER)]
 
−
|2005-2016
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#R-CHOP|R-CHOP]] x 4
 
−
| style="background-color:#eeee01" |Non-inferior PFS36
 
−
| style="background-color:#d73027" |More toxic
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5278952/ Oki et al. 2013 (MDACC 2005-0054)]
 
−
|2005-NR
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 
−
|[[#R-Hyper-CVAD.2FR-MA|R-Hyper-CVAD/R-MA]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior CRR
 
−
|
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116833/ Seymour et al. 2014 (MAIN)]
 
−
|2007-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#RA-CHOP-21_99|RA-CHOP-21]]
 
−
| style="background-color:#ffffbf" |Did not meet secondary endpoint of PFS
 
−
| style="background-color:#1a9850" |Better cardiac safety
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2017.73.2784 Leonard et al. 2017 (C05013)]
 
−
|2009-2013
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 
−
|[[Diffuse_large_B-cell_lymphoma_-_historical#VR-CHOP|VR-CHOP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2017.73.3402 Vitolo et al. 2017 (GOYA)]
 
−
|2011-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#G-CHOP_99|G-CHOP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6553835/ Younes et al. 2019 (PHOENIX)]
 
−
|2013-2015
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#IR-CHOP_99|IR-CHOP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1200/jco.20.01366 Nowakowski et al. 2021 (ROBUST)]
 
−
|2015-2017
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#R2-CHOP|R2-CHOP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|
 
−
|-
 
−
|}
 
−
''<sup>1</sup>While the primary endpoint in PIX203 was inconclusive (non-inferiority by CR/CRu rate), this arm seemed to have superior OS.''<br>
 
−
''Note: patients in Vose et al. 2001 received rituximab 2 days before CHOP, i.e., all CHOP days are moved forward by 2 days. Patients in GOYA received 8 doses of rituximab, regardless of the number of chemotherapy cycles given. Patients in FLYER were 18 to 60 and had no risk factors according to age-adjusted IPI. Patients in ROBUST could receive two additional cycles of rituximab (8 total), per local practices.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg IV or PO once per day on days 1 to 5
 
−
====Supportive therapy====
 
−
*Varies per protocol
 
−
*Prophylactic [[:Category:Granulocyte colony-stimulating factors|G-CSF]] used for persisting grade 4 neutropenia or febrile neutropenia.
 
−
*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|Cotrimoxazole]] (dose/schedule not specified) prophylaxis.
 
−
*Erythropoietin use was allowed for hemoglobin less than 11 g/dL.
 
−
'''21-day cycle for 6 to 8 cycles (see note)'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Some protocols: [[#Radiation_therapy|Radiation therapy]] was scheduled for sites of previous bulky disease or partially responding sites
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #5, prednisone 100 mg, capped vincristine, 6+2 cycles {{#subobject:e3dfg1|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa2115304 Tilly et al. 2021 (POLARIX)]
 
−
|2017-2019
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Pola-R-CHP|Pola-R-CHP]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 1 to 6: 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] as follows:
 
−
**Cycles 1 to 6: 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] as follows:
 
−
**Cycles 1 to 6: 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] as follows:
 
−
**Cycles 1 to 6: 100 mg PO once per day on days 1 to 5
 
−
'''21-day cycle for 8 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #6, prednisone 100 mg, flat-dose vincristine {{#subobject:bcb2bf|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045%2806%2970664-7 Pfreundschuh et al. 2006 (NCIC-CTG LY.9)]
 
−
|2000-2003
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|1. [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]]<br> 2. [[Diffuse_large_B-cell_lymphoma_-_historical#CHOEP-21|CHOEP-21]]<br> 3. [[Diffuse_large_B-cell_lymphoma_-_historical#MACOP-B|MACOP-B]]<br> 4. [[Diffuse_large_B-cell_lymphoma_-_historical#PMitCEBO|PMitCEBO]]
 
−
| style="background-color:#1a9850" |Superior EFS<sup>1</sup><br>EFS72: 74.3% vs 55.8%
 
−
| style="background-color:#eeee01" |Similar toxicity
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2011 update.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
====Supportive therapy====
 
−
*G-CSF with one of the following:
 
−
**[[Filgrastim (Neupogen)]] used at physician discretion for neutropenia
 
−
**[[Lenograstim (Granocyte)]] used at physician discretion for neutropenia
 
−
'''21-day cycle for 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#Radiation_therapy|Radiation therapy]] 30 to 40 Gy given to sites of primary bulky disease; 30 to 40 Gy to primary extranodal disease at physician discretion
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #7, prednisone 100 mg/m<sup>2</sup> {{#subobject:e3dfe2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4616024/ Offner et al. 2015 (LYM-2034)]
 
−
|2010-2011
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 
−
|[[#VR-CAP_99|VR-CAP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of CR rate
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Biomarker eligibility criteria====
 
−
*Non-germinal center B-cell (non-GCB) DLBCL
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
'''21-day cycle for 6 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #8, rituximab lead-in {{#subobject:f05383|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.05.1003 Habermann et al. 2006 (ECOG E4494)]
 
−
|1998-2001
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]]
 
−
| style="background-color:#91cf60" |Seems to have superior FFS
 
−
|-
 
−
|}
 
−
''Note: an advantage for maintenance was only seen in the group receiving [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]] upfront, which is no longer standard of care.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days -7 & -3
 
−
**Cycle 2 onwards: 375 mg/m<sup>2</sup> IV once on day -2
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
====Supportive therapy====
 
−
*Recommended: [[Filgrastim (Neupogen)]] "according to guidelines"
 
−
'''21-day cycle for 6 to 8 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#Rituximab_monotherapy|Rituximab]] maintenance versus [[Diffuse_large_B-cell_lymphoma_-_null_regimens#Observation|observation]]
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #9, short-course for early stage DLBCL {{#subobject:caca45|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2007.13.6929 Persky et al. 2008 (SWOG S0014)]
 
−
|2000-2002
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355104/ Yoon et al. 2017 (CISL 12-09)]
 
−
|2010-2013
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Note: CISL 12-09 does not have dosing details.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*CISL 12-09: [[Surgery#Surgical_resection|Surgical resection]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Prephase: 375 mg/m<sup>2</sup> IV once on day -7
 
−
**Cycles 1 to 3: 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
'''21-day cycle for 3 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*SWOG S0014: [[#Radiation_therapy|IFRT]] to begin 3 weeks after last cycle of R-CHOP
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #10, primary testicular DLBCL {{#subobject:7f4db5|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2010.31.4187 Vitolo et al. 2011 (IELSG-10)]
 
−
|2001-2006
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Note: This regimen a component of a sequential treatment protocol.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Eligibility criteria====
 
−
*Primary testicular lymphoma
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*Diagnostic [[Surgery#Orchiectomy|orchiectomy]] prior to starting chemotherapy
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 0 or 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
'''21-day cycle for 6 cycles (up to 8 cycles for stage II patients)'''
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] 12 mg IT once per day on days 1, 8, 15, 22
 
−
'''4-week course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#Radiation_therapy|RT]]
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
  
−
===Regimen variant #11, 2 cycles with response adaptation {{#subobject:d56c17|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691189/ Witzig et al. 2015 (ECOG E3402)]
 
−
|2004-2008
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Eligibility criteria====
 
−
*Stage I-II DLBCL based on CT (not PET-CT) imaging
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
'''21-day cycle for 2 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*CR based on '''CT''' scan: R-CHOP x 2 (4 cycles total), then [[#Ibritumomab_tiuxetan_protocol|ibritumomab tiuxetan]] consolidation
 
−
*CRu or PR based on '''CT''' scan: R-CHOP x 4 (6 cycles total), then [[#Ibritumomab_tiuxetan_protocol|ibritumomab tiuxetan]] consolidation
 
−
</div></div>
 
−
===References===
 
−
#Vose JM, Link BK, Grossbard ML, Czuczman M, Grillo-Lopez A, Gilman P, Lowe A, Kunkel LA, Fisher RI. Phase II study of rituximab in combination with CHOP chemotherapy in patients with previously untreated, aggressive non-Hodgkin's lymphoma. J Clin Oncol. 2001 Jan 15;19(2):389-97. [https://doi.org/10.1200/JCO.2001.19.2.389 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11208830 PubMed]
 
−
#'''LNH 98-5:''' Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C; Groupe d'Etude des Lymphomes de l'Adulte. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002 Jan 24;346(4):235-42. [https://doi.org/10.1056/NEJMoa011795 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11807147 PubMed]
 
−
##'''Update:''' Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Fermé C, Christian B, Lepage E, Tilly H, Morschhauser F, Gaulard P, Salles G, Bosly A, Gisselbrecht C, Reyes F, Coiffier B. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2005 Jun 20;23(18):4117-26. [https://doi.org/10.1200/jco.2005.09.131 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15867204 PubMed]
 
−
##'''Update:''' Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S, Lefort S, Marit G, Macro M, Sebban C, Belhadj K, Bordessoule D, Fermé C, Tilly H. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d'Etudes des Lymphomes de l'Adulte. Blood. 2010 Sep 23;116(12):2040-5. [http://www.bloodjournal.org/content/116/12/2040.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2951853/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20548096 PubMed] content property of [http://hemonc.org HemOnc.org]
 
−
##'''Update:''' Mounier N, Heutte N, Thieblemont C, Briere J, Gaulard P, Feugier P, Ghesquieres H, Van Den Neste E, Robu D, Tilly H, Bouabdallah R, Safar V, Coiffier B; Groupe d'Etude des Lymphomes de l'Adulte (GELA). Ten-year relative survival and causes of death in elderly patients treated with R-CHOP or CHOP in the GELA LNH-985 trial. Clin Lymphoma Myeloma Leuk. 2012 Jun;12(3):151-4. Epub 2012 Feb 1. [http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(11)00607-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22301063 PubMed]
 
−
#'''NCIC-CTG LY.9:''' Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. [https://doi.org/10.1016/S1470-2045%2806%2970664-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16648042 PubMed] NCT00064116
 
−
##'''Update:''' Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, López-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N; MabThera International Trial (MInT) Group. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011 Oct;12(11):1013-22. [https://doi.org/10.1016/S1470-2045%2811%2970235-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21940214 PubMed]
 
−
#'''ECOG E4494:''' Habermann TM, Weller EA, Morrison VA, Gascoyne RD, Cassileth PA, Cohn JB, Dakhil SR, Woda B, Fisher RI, Peterson BA, Horning SJ. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006 Jul 1;24(19):3121-7. Epub 2006 Jun 5. [https://doi.org/10.1200/jco.2005.05.1003 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16754935 PubMed] NCT00003150
 
−
#'''SWOG S0014:''' Persky DO, Unger JM, Spier CM, Stea B, LeBlanc M, McCarty MJ, Rimsza LM, Fisher RI, Miller TP; [[Study_Groups#SWOG|SWOG]]. Phase II study of rituximab plus three cycles of CHOP and involved-field radiotherapy for patients with limited-stage aggressive B-cell lymphoma: Southwest Oncology Group study 0014. J Clin Oncol. 2008 May 10;26(14):2258-63. Epub 2008 Apr 14. [https://doi.org/10.1200/jco.2007.13.6929 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18413640 PubMed]
 
−
#'''IELSG-10:''' Vitolo U, Chiappella A, Ferreri AJ, Martelli M, Baldi I, Balzarotti M, Bottelli C, Conconi A, Gomez H, Lopez-Guillermo A, Martinelli G, Merli F, Novero D, Orsucci L, Pavone V, Ricardi U, Storti S, Gospodarowicz MK, Cavalli F, Sarris AH, Zucca E. First-line treatment for primary testicular diffuse large B-cell lymphoma with rituximab-CHOP, CNS prophylaxis, and contralateral testis irradiation: final results of an international phase II trial. J Clin Oncol. 2011 Jul 10;29(20):2766-72. Epub 2011 Jun 6. [https://doi.org/10.1200/jco.2010.31.4187 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21646602 PubMed] NCT00210379
 
−
#'''ANZINTER3:''' Merli F, Luminari S, Rossi G, Mammi C, Marcheselli L, Tucci A, Ilariucci F, Chiappella A, Musso M, Di Rocco A, Stelitano C, Alvarez I, Baldini L, Mazza P, Salvi F, Arcari A, Fragasso A, Gobbi PG, Liberati AM, Federico M. Cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab versus epirubicin, cyclophosphamide, vinblastine, prednisone and rituximab for the initial treatment of elderly "fit" patients with diffuse large B-cell lymphoma: results from the ANZINTER3 trial of the Intergruppo Italiano Linfomi. Leuk Lymphoma. 2012 Apr;53(4):581-8. Epub 2011 Nov 15. [https://doi.org/10.3109/10428194.2011.621565 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21895543 PubMed] NCT01148446
 
−
#'''LNH03-2B:''' Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O, Thiéblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquières H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais JP, Salles G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011 Nov 26;378(9806):1858-67. [https://doi.org/10.1016/S0140-6736(11)61040-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22118442 PubMed] NCT00140595
 
−
##'''Subgroup analysis:''' Molina TJ, Canioni D, Copie-Bergman C, Recher C, Brière J, Haioun C, Berger F, Fermé C, Copin MC, Casasnovas O, Thieblemont C, Petrella T, Leroy K, Salles G, Fabiani B, Morschauser F, Mounier N, Coiffier B, Jardin F, Gaulard P, Jais JP, Tilly H. Young patients with non-germinal center B-cell-like diffuse large B-cell lymphoma benefit from intensified chemotherapy with ACVBP plus rituximab compared with CHOP plus rituximab: analysis of data from the Groupe d'Etudes des Lymphomes de l'Adulte/lymphoma study association phase III trial LNH 03-2B. J Clin Oncol. 2014 Dec 10;32(35):3996-4003. Epub 2014 Nov 10. [https://doi.org/10.1200/JCO.2013.54.9493 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25385729 PubMed]
 
−
#'''LNH03-6B:''' Delarue R, Tilly H, Mounier N, Petrella T, Salles G, Thieblemont C, Bologna S, Ghesquières H, Hacini M, Fruchart C, Ysebaert L, Fermé C, Casasnovas O, Van Hoof A, Thyss A, Delmer A, Fitoussi O, Molina TJ, Haioun C, Bosly A. Dose-dense rituximab-CHOP compared with standard rituximab-CHOP in elderly patients with diffuse large B-cell lymphoma (the LNH03-6B study): a randomised phase 3 trial. Lancet Oncol. 2013 May;14(6):525-33. Epub 2013 Apr 9. [https://doi.org/10.1016/S1470-2045(13)70122-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23578722 PubMed] NCT00144755
 
−
#'''PIX203:''' Herbrecht R, Cernohous P, Engert A, Le Gouill S, Macdonald D, Machida C, Myint H, Saleh A, Singer J, Wilhelm M, van der Jagt R. Comparison of pixantrone-based regimen (CPOP-R) with doxorubicin-based therapy (CHOP-R) for treatment of diffuse large B-cell lymphoma. Ann Oncol. 2013 Oct;24(10):2618-23. Epub 2013 Aug 14. [https://doi.org/10.1093/annonc/mdt289 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/23946328 PubMed] NCT00268853
 
−
#'''MDACC 2005-0054:''' Oki Y, Westin JR, Vega F, Chuang H, Fowler N, Neelapu S, Hagemeister FB, McLaughlin P, Kwak LW, Romaguera JE, Fanale M, Younes A, Rodriguez MA, Orlowski RZ, Wang M, Ouzounian ST, Samaniego F, Fayad L. Prospective phase II study of rituximab with alternating cycles of hyper-CVAD and high-dose methotrexate with cytarabine for young patients with high-risk diffuse large B-cell lymphoma. Br J Haematol. 2013 Dec;163(5):611-20. Epub 2013 Oct 1. [https://doi.org/10.1111/bjh.12585 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5278952/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24117234 PubMed] NCT00290498
 
−
#'''SWOG S9704:''' Stiff PJ, Unger JM, Cook JR, Constine LS, Couban S, Stewart DA, Shea TC, Porcu P, Winter JN, Kahl BS, Miller TP, Tubbs RR, Marcellus D, Friedberg JW, Barton KP, Mills GM, LeBlanc M, Rimsza LM, Forman SJ, Fisher RI. Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma. N Engl J Med. 2013 Oct 31;369(18):1681-90. [https://doi.org/10.1056/NEJMoa1301077 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985418/ link to PMC article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/24171516 PubMed] NCT00004031
 
−
##'''Subgroup analysis:''' Puvvada SD, Stiff PJ, Leblanc M, Cook JR, Couban S, Leonard JP, Kahl B, Marcellus D, Shea TC, Winter JN, Li H, Rimsza LM, Friedberg JW, Smith SM. Outcomes of MYC-associated lymphomas after R-CHOP with and without consolidative autologous stem cell transplant: subset analysis of randomized trial intergroup SWOG S9704. Br J Haematol. 2016 Sep;174(5):686-91. Epub 2016 Apr 13. [https://doi.org/10.1111/bjh.14100 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125530/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27072903 PubMed]
 
−
#'''MAIN:''' Seymour JF, Pfreundschuh M, Trnený M, Sehn LH, Catalano J, Csinady E, Moore N, Coiffier B; MAIN Study Investigators. R-CHOP with or without bevacizumab in patients with previously untreated diffuse large B-cell lymphoma: final MAIN study outcomes. Haematologica. 2014 Aug;99(8):1343-9. Epub 2014 Jun 3. [http://www.haematologica.org/content/99/8/1343.abstract link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116833/ link to PMC article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/24895339 PubMed] NCT00486759
 
−
<!-- Prior publication: Poster presentation at the 2014 annual meeting of the American Society of Hematology (Howlett C, Landsburg DJ, Chong EA, Snedecor SJ, Schuster SJ, Green TM, Cohen JB, Svoboda J, Nasta SD, Feldman T, Rago R, Land D, Walsh KM, Goy A, Mato AR. Front-line, dose-escalated immunochemotherapy is associated with a significant PFS (but not OS) advantage in 401 patients (pts) with double-hit lymphomas (DHL): A systematic review and meta-analysis. Blood, 124, abst 3056). -->
 
−
#'''Retrospective:''' Howlett C, Snedecor SJ, Landsburg DJ, Svoboda J, Chong EA, Schuster SJ, Nasta SD, Feldman T, Rago A, Walsh KM, Weber S, Goy A, Mato A. Front-line, dose-escalated immunochemotherapy is associated with a significant progression-free survival advantage in patients with double-hit lymphomas: a systematic review and meta-analysis. Br J Haematol. 2015 Aug;170(4):504-14. Epub 2015 Apr 24. [https://doi.org/10.1111/bjh.13463 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25907897 PubMed]
 
−
#'''ECOG E3402:''' Witzig TE, Hong F, Micallef IN, Gascoyne RD, Dogan A, Wagner H Jr, Kahl BS, Advani RH, Horning SJ. A phase II trial of RCHOP followed by radioimmunotherapy for early stage (stages I/II) diffuse large B-cell non-Hodgkin lymphoma: ECOG3402. Br J Haematol. 2015 Sep;170(5):679-86. Epub 2015 May 14. [https://doi.org/10.1111/bjh.13493 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691189/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25974212 PubMed] NCT00088881
 
−
#'''LYM-2034:''' Offner F, Samoilova O, Osmanov E, Eom HS, Topp MS, Raposo J, Pavlov V, Ricci D, Chaturvedi S, Zhu E, van de Velde H, Enny C, Rizo A, Ferhanoglu B. Frontline rituximab, cyclophosphamide, doxorubicin, and prednisone with bortezomib (VR-CAP) or vincristine (R-CHOP) for non-GCB DLBCL. Blood. 2015 Oct 15;126(16):1893-901. Epub 2015 Jul 31. [http://www.bloodjournal.org/content/126/16/1893.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4616024/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26232170 PubMed] NCT01040871
 
−
#'''CISL 12-09:''' Yoon DH, Sohn BS, Oh SY, Lee WS, Lee SM, Yang DH, Huh J, Suh C. Feasibility of abbreviated cycles of immunochemotherapy for completely resected limited-stage CD20+ diffuse large B-cell lymphoma (CISL 12-09). Oncotarget. 2017 Feb 21;8(8):13367-13374. [https://doi.org/10.18632/oncotarget.14531 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355104/ link to PMC article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/28076329 PubMed] NCT01279902
 
−
#'''MabEase:''' Lugtenburg P, Avivi I, Berenschot H, Ilhan O, Marolleau JP, Nagler A, Rueda A, Tani M, Turgut M, Osborne S, Smith R, Pfreundschuh M. Efficacy and safety of subcutaneous and intravenous rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in first-line diffuse large B-cell lymphoma: the randomized MabEase study. Haematologica. 2017 Nov;102(11):1913-1922. Epub 2017 Sep 21. [http://www.haematologica.org/content/102/11/1913 link to original article] '''contains partial protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664395/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28935843 PubMed] NCT01649856
 
−
#'''GOYA:''' Vitolo U, Trněný M, Belada D, Burke JM, Carella AM, Chua N, Abrisqueta P, Demeter J, Flinn I, Hong X, Kim WS, Pinto A, Shi YK, Tatsumi Y, Oestergaard MZ, Wenger M, Fingerle-Rowson G, Catalani O, Nielsen T, Martelli M, Sehn LH. Obinutuzumab or rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in previously untreated diffuse large B-cell lymphoma. J Clin Oncol. 2017 Nov 1;35(31):3529-3537. Epub 2017 Aug 10. [https://doi.org/10.1200/JCO.2017.73.3402 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28796588 PubMed] NCT01287741
 
−
##'''Update:''' Sehn LH, Martelli M, Trněný M, Liu W, Bolen CR, Knapp A, Sahin D, Sellam G, Vitolo U. A randomized, open-label, Phase III study of obinutuzumab or rituximab plus CHOP in patients with previously untreated diffuse large B-Cell lymphoma: final analysis of GOYA. J Hematol Oncol. 2020 Jun 6;13(1):71. [https://doi.org/10.1186/s13045-020-00900-7 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7276080/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32505213/ PubMed]
 
−
#'''C05013:''' Leonard JP, Kolibaba KS, Reeves JA, Tulpule A, Flinn IW, Kolevska T, Robles R, Flowers CR, Collins R, DiBella NJ, Papish SW, Venugopal P, Horodner A, Tabatabai A, Hajdenberg J, Park J, Neuwirth R, Mulligan G, Suryanarayan K, Esseltine DL, de Vos S. Randomized phase II study of R-CHOP with or without bortezomib in previously untreated patients with non-germinal center B-cell-like diffuse large B-cell lymphoma. J Clin Oncol. 2017 Nov 1;35(31):3538-3546. Epub 2017 Sep 1. [https://doi.org/10.1200/JCO.2017.73.2784 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28862883 PubMed] NCT00931918
 
−
#'''CSWOG0001:''' Li X, Huang H, Xu B, Guo H, Lin Y, Ye S, Yi J, Li W, Wu X, Wang W, Zhan H, Xie D, Peng J, Cao Y, Pu X, Guo C, Hong H, Wang Z, Fang X, Zhou Y, Lin S, Liu Q, Lin T. Dose-Dense Rituximab-CHOP versus Standard Rituximab-CHOP in Newly Diagnosed Chinese Patients with Diffuse Large B-Cell Lymphoma: A Randomized, Multicenter, Open-Label Phase 3 Trial. Cancer Res Treat. 2019 Jul;51(3):919-932. Epub 2018 Oct 2. [https://doi.org/10.4143/crt.2018.230 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639223/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30282447 PubMed] NCT01793844
 
−
#'''PHOENIX:''' Younes A, Sehn LH, Johnson P, Zinzani PL, Hong X, Zhu J, Patti C, Belada D, Samoilova O, Suh C, Leppä S, Rai S, Turgut M, Jurczak W, Cheung MC, Gurion R, Yeh SP, Lopez-Hernandez A, Dührsen U, Thieblemont C, Chiattone CS, Balasubramanian S, Carey J, Liu G, Shreeve SM, Sun S, Zhuang SH, Vermeulen J, Staudt LM, Wilson W; PHOENIX investigators. Randomized phase III trial of ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in non-germinal center B-cell diffuse large B-cell lymphoma. J Clin Oncol. 2019 May 20;37(15):1285-1295. Epub 2019 Mar 22. [https://doi.org/10.1200/JCO.18.02403 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6553835/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30901302 PubMed] NCT01855750
 
−
<!-- # '''Abstract:''' Wyndham H. Wilson, MD, PhD, Jung sin-Ho, Brandelyn Nicole Pitcher, MS, Eric D Hsi, MD, Jonathan Friedberg, MD, Bruce Cheson, MD, Nancy L Bartlett, MD, Scott Smith, Nina Wagner Johnston, MD, Brad S Kahl, Louis M. Staudt, MD, PhD, Kristie Blum, MD, Jeremy Abramson, Oliver W Press, MD, PhD, Richard I. Fisher, MD, Kristy L. Richards, PhD, MD, Heiko Schoder, MD, Julie E Chang, Andrew D. Zelenetz and John P. Leonard, MD. Phase III Randomized Study of R-CHOP Versus DA-EPOCH-R and Molecular Analysis of Untreated Diffuse Large B-Cell Lymphoma: CALGB/Alliance 50303. ASH 2016 Abstract 469 [https://ashpublications.org/blood/article/128/22/469/101297/Phase-III-Randomized-Study-of-R-CHOP-Versus-DA link to abstract] -->
 
−
#'''CALGB 50303:''' Bartlett NL, Wilson WH, Jung SH, Hsi ED, Maurer MJ, Pederson LD, Polley MC, Pitcher BN, Cheson BD, Kahl BS, Friedberg JW, Staudt LM, Wagner-Johnston ND, Blum KA, Abramson JS, Reddy NM, Winter JN, Chang JE, Gopal AK, Chadburn A, Mathew S, Fisher RI, Richards KL, Schöder H, Zelenetz AD, Leonard JP. Dose-Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303. J Clin Oncol. 2019 Jul 20;37(21):1790-1799. Epub 2019 Apr 2. [https://doi.org/10.1200/JCO.18.01994 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6774813/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30939090 PubMed] NCT00118209
 
−
#'''FLYER:''' Poeschel V, Held G, Ziepert M, Witzens-Harig M, Holte H, Thurner L, Borchmann P, Viardot A, Soekler M, Keller U, Schmidt C, Truemper L, Mahlberg R, Marks R, Hoeffkes HG, Metzner B, Dierlamm J, Frickhofen N, Haenel M, Neubauer A, Kneba M, Merli F, Tucci A, de Nully Brown P, Federico M, Lengfelder E, di Rocco A, Trappe R, Rosenwald A, Berdel C, Maisenhoelder M, Shpilberg O, Amam J, Christofyllakis K, Hartmann F, Murawski N, Stilgenbauer S, Nickelsen M, Wulf G, Glass B, Schmitz N, Altmann B, Loeffler M, Pfreundschuh M; FLYER Trial Investigators; German Lymphoma Alliance. Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER): a randomised, phase 3, non-inferiority trial. Lancet. 2019 Dec 21;394(10216):2271-2281. [https://doi.org/10.1016/S0140-6736(19)33008-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/31868632 PubMed] NCT00278421
 
−
#'''ROBUST:''' Nowakowski GS, Chiappella A, Gascoyne RD, Scott DW, Zhang Q, Jurczak W, Özcan M, Hong X, Zhu J, Jin J, Belada D, Bergua JM, Piazza F, Mócikova H, Molinari AL, Yoon DH, Cavallo F, Tani M, Yamamoto K, Izutsu K, Kato K, Czuczman M, Hersey S, Kilcoyne A, Russo J, Hudak K, Zhang J, Wade S, Witzig TE, Vitolo U. ROBUST: A Phase III Study of Lenalidomide Plus R-CHOP Versus Placebo Plus R-CHOP in Previously Untreated Patients With ABC-Type Diffuse Large B-Cell Lymphoma. J Clin Oncol. 2021 Apr 20;39(12):1317-1328. Epub 2021 Feb 23. [https://doi.org/10.1200/jco.20.01366 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33621109/ PubMed] NCT02285062
 
−
#'''POLARIX:''' Tilly H, Morschhauser F, Sehn LH, Friedberg JW, Trněný M, Sharman JP, Herbaux C, Burke JM, Matasar M, Rai S, Izutsu K, Mehta-Shah N, Oberic L, Chauchet A, Jurczak W, Song Y, Greil R, Mykhalska L, Bergua-Burgués JM, Cheung MC, Pinto A, Shin HJ, Hapgood G, Munhoz E, Abrisqueta P, Gau JP, Hirata J, Jiang Y, Yan M, Lee C, Flowers CR, Salles G. Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. N Engl J Med. 2022 Jan 27;386(4):351-363. Epub 2021 Dec 14. [https://doi.org/10.1056/nejmoa2115304 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34904799/ PubMed] NCT03274492
 
−
#'''ESCALADE:''' NCT04529772
 
−
#'''frontMIND:''' NCT04824092
 
−
==R-CHOP (Prednisolone) {{#subobject:875cc2|Regimen=1}}==
 
−
R-CHOP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisolone
 
−
===Example orders===
 
−
*[[Example orders for R-CHOP in lymphoma]]
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, prednisolone 40 mg/m<sup>2</sup>, 8 cycles {{#subobject:74f424|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(13)60313-X Cunningham et al. 2013 (UK NCRI R-CHOP14v21)]
 
−
|2005-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#R-CHOP-14_.28Prednisolone.29|R-CHOP-14]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|
 
−
|-
 
−
|[https://www.ejcancer.com/article/S0959-8049(16)00088-5 Fridrik et al. 2016 (AGMT NHL-14)]
 
−
|2007-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#R-COMP_99|R-COMP]]
 
−
| style="background-color:#ffffbf" |Did not meet secondary efficacy endpoints
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of reduced cardiotoxicity
 
−
|-
 
−
|}
 
−
''Note: Cunningham et al. 2013 states that the regimen is based on LNH 98-5, but notably it uses prednisolone instead of prednisone. AGMT NHL-14 states that R-CHOP was "given in standard doses" per LNH 98-5, but this regimen uses prednisone, whereas the title and text of Fridrik et al. 2016 implies that prednisolone was used. The authors have confirmed that prednisolone was used, due to prednisone not being available in Austria.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisolone (Millipred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
====CNS therapy, prophylaxis====
 
−
Per investigator discretion, but Cunningham et al. 2013 recommended that patients who had involvement of the "bone marrow, peripheral blood, nasal or paranasal sinuses, orbit, and testis" (they probably intended to say "or testis") receive:
 
−
*[[Methotrexate (MTX)]] 12.5 mg IT "for the first three cycles of treatment, administered as per local guidelines." No other details given.
 
−
====Supportive therapy====
 
−
*Described in Cunningham et al. 2013
 
−
*[[Lenograstim (Granocyte)]] (dose/route not specified) given on days 4 to 12 at physician discretion
 
−
*[[Allopurinol (Zyloprim)]] 300 mg PO once per day during cycle 1
 
−
*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|Co-trimoxazole]] 80/400 mg PO twice per day on 3 days per week, taken throughout therapy, ending 2 weeks after chemotherapy is completed
 
−
'''21-day cycle for 8 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, prednisolone 60 mg/m<sup>2</sup>, 6 + 2 cycles {{#subobject:74ug81|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1182/bloodadvances.2020002567 Ohmachi et al. 2021 (JCOG0601)]
 
−
|2007-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#R-CHOP|R-CHOP]]; weekly rituximab
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|}
 
−
''Note: This regimen was intended for stage I nonbulky patients who were at least 65 years old.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 1 to 6: 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] as follows:
 
−
**Cycles 1 to 6: 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] as follows:
 
−
**Cycles 1 to 6: 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisolone (Millipred)]] as follows:
 
−
**Cycles 1 to 6: 60 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
'''21-day cycle for 8 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, prednisolone 60 mg/m<sup>2</sup>, 8 cycles {{#subobject:74ug71|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1182/bloodadvances.2020002567 Ohmachi et al. 2021 (JCOG0601)]
 
−
|2007-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#R-CHOP|R-CHOP]]; weekly rituximab
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|}
 
−
''Note: This regimen was intended for stage I bulky and stage II to IV patients who were at least 65 years old.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisolone (Millipred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
'''21-day cycle for 8 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #4, prednisolone 100 mg, 4 + 2 cycles {{#subobject:1cbzib|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(19)33008-9 Poeschel et al. 2019 (FLYER)]
 
−
|2005-2016
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|[[#R-CHOP|R-CHOP]] x 6
 
−
| style="background-color:#eeee01" |Non-inferior PFS<br>PFS36: 96% vs 93%
 
−
| style="background-color:#1a9850" |Less toxic
 
−
|-
 
−
|}
 
−
''Note: Patients in FLYER were 18 to 60 and had no risk factors according to age-adjusted IPI.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 1 to 4: 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] as follows:
 
−
**Cycles 1 to 4: 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] as follows:
 
−
**Cycles 1 to 4: 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisolone (Millipred)]] as follows:
 
−
**Cycles 1 to 4: 100 mg IV or PO once per day on days 1 to 5
 
−
'''21-day cycle for 6 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #5, prednisolone 100 mg, 6 cycles {{#subobject:74f454|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(19)33008-9 Poeschel et al. 2019 (FLYER)]
 
−
|2005-2016
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#R-CHOP|R-CHOP]] x 4
 
−
| style="background-color:#eeee01" |Non-inferior PFS36
 
−
| style="background-color:#d73027" |More toxic
 
−
|-
 
−
|[https://doi.org/10.7314/apjcp.2016.17.3.1513 Payandeh et al. 2016]
 
−
|2011-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#R-CHOP-14_.28Prednisolone.29|R-CHOP-14]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494978/ Davies et al. 2019 (REMoDL-B)]
 
−
|2011-2015
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Diffuse_large_B-cell_lymphoma_-_historical#VR-CHOP|RB-CHOP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS30
 
−
|
 
−
|-
 
−
|}
 
−
''Note: this was the lower bound of cycles specified by Payandeh et al. 2016.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisolone (Millipred)]] 100 mg PO once per day on days 1 to 5
 
−
'''21-day cycle for 6 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #6, prednisolone 100 mg, 6 + 2 cycles {{#subobject:7hu181|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1182/bloodadvances.2020002567 Ohmachi et al. 2021 (JCOG0601)]
 
−
|2007-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#R-CHOP|R-CHOP]]; weekly rituximab
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|}
 
−
''Note: This regimen was intended for stage I nonbulky patients who were younger than 65 years old.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 1 to 6: 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] as follows:
 
−
**Cycles 1 to 6: 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] as follows:
 
−
**Cycles 1 to 6: 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisolone (Millipred)]] as follows:
 
−
**Cycles 1 to 6: 100 mg PO once per day on days 1 to 5
 
−
'''21-day cycle for 8 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #7, prednisolone 100 mg, 8 cycles {{#subobject:74f454|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1182/bloodadvances.2020002567 Ohmachi et al. 2021 (JCOG0601)]
 
−
|2007-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#R-CHOP|R-CHOP]]; weekly rituximab
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|[https://doi.org/10.7314/apjcp.2016.17.3.1513 Payandeh et al. 2016]
 
−
|2011-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#R-CHOP-14_.28Prednisolone.29|R-CHOP-14]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|}
 
−
''Note: This was the upper bound of cycles specified by Payandeh et al. 2016. In JCOG0601, this regimen was intended for stage I bulky and stage II to IV patients who were younger than 65 years old.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisolone (Millipred)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
'''21-day cycle for 8 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''UK NCRI R-CHOP14v21:''' Cunningham D, Hawkes EA, Jack A, Qian W, Smith P, Mouncey P, Pocock C, Ardeshna KM, Radford JA, McMillan A, Davies J, Turner D, Kruger A, Johnson P, Gambell J, Linch D. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles. Lancet. 2013 May 25;381(9880):1817-26. Epub 2013 Apr 22. [https://doi.org/10.1016/S0140-6736(13)60313-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23615461 PubMed] ISRCTN16017947
 
−
#'''AGMT NHL-14:''' Fridrik MA, Jaeger U, Petzer A, Willenbacher W, Keil F, Lang A, Andel J, Burgstaller S, Krieger O, Oberaigner W, Sihorsch K, Greil R; Arbeitsgemeinschaft Medikamentöse Tumortherapie. Cardiotoxicity with rituximab, cyclophosphamide, non-pegylated liposomal doxorubicin, vincristine and prednisolone compared to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone in frontline treatment of patients with diffuse large B-cell lymphoma: a randomised phase-III study from the Austrian Cancer Drug Therapy Working Group (NHL-14). Eur J Cancer. 2016 May;58:112-21. Epub 2016 Mar 15. [https://www.ejcancer.com/article/S0959-8049(16)00088-5 link to original article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/26990931 PubMed] NCT00575406
 
−
#Payandeh M, Najafi S, Shojaiyan FZ, Sadeghi M. Phase III of study of R-CHOP-21 vs R-CHOP-14 for untreated stage III and IV B-cell non-Hodgkin's lymphoma: a report from Iran. Asian Pac J Cancer Prev. 2016;17(3):1513-7. [https://doi.org/10.7314/apjcp.2016.17.3.1513 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27039799 PubMed]
 
−
#'''REMoDL-B:''' Davies A, Cummin TE, Barrans S, Maishman T, Mamot C, Novak U, Caddy J, Stanton L, Kazmi-Stokes S, McMillan A, Fields P, Pocock C, Collins GP, Stephens R, Cucco F, Clipson A, Sha C, Tooze R, Care MA, Griffiths G, Du MQ, Westhead DR, Burton C, Johnson PWM. Gene-expression profiling of bortezomib added to standard chemoimmunotherapy for diffuse large B-cell lymphoma (REMoDL-B): an open-label, randomised, phase 3 trial. Lancet Oncol. 2019 May;20(5):649-662. Epub 2019 Apr 1. [https://doi.org/10.1016/S1470-2045(18)30935-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494978/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30948276 PubMed] NCT01324596
 
−
#'''FLYER:''' Poeschel V, Held G, Ziepert M, Witzens-Harig M, Holte H, Thurner L, Borchmann P, Viardot A, Soekler M, Keller U, Schmidt C, Truemper L, Mahlberg R, Marks R, Hoeffkes HG, Metzner B, Dierlamm J, Frickhofen N, Haenel M, Neubauer A, Kneba M, Merli F, Tucci A, de Nully Brown P, Federico M, Lengfelder E, di Rocco A, Trappe R, Rosenwald A, Berdel C, Maisenhoelder M, Shpilberg O, Amam J, Christofyllakis K, Hartmann F, Murawski N, Stilgenbauer S, Nickelsen M, Wulf G, Glass B, Schmitz N, Altmann B, Loeffler M, Pfreundschuh M; FLYER Trial Investigators; German Lymphoma Alliance. Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER): a randomised, phase 3, non-inferiority trial. Lancet. 2019 Dec 21;394(10216):2271-2281. [https://doi.org/10.1016/S0140-6736(19)33008-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/31868632 PubMed] NCT00278421
 
−
#'''JCOG0601:''' Ohmachi K, Kinoshita T, Tobinai K, Ogawa G, Mizutani T, Yamauchi N, Fukuhara N, Uchida T, Yamamoto K, Miyazaki K, Tsukamoto N, Iida S, Utsumi T, Yoshida I, Imaizumi Y, Tokunaga T, Yoshida S, Masaki Y, Murayama T, Yakushijin Y, Suehiro Y, Nosaka K, Dobashi N, Kuroda J, Takamatsu Y, Maruyama D, Ando K, Ishizawa K, Ogura M, Yoshino T, Hotta T, Tsukasaki K, Nagai H; Japan Clinical Oncology Group. A randomized phase 2/3 study of R-CHOP vs CHOP combined with dose-dense rituximab for DLBCL: the JCOG0601 trial. Blood Adv. 2021 Feb 23;5(4):984-993. [https://doi.org/10.1182/bloodadvances.2020002567 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33591324/ PubMed] jRCTs031180139
 
−
==R-CHOP (Rituximab and hyaluronidase) {{#subobject:98gxb2|Regimen=1}}==
 
−
R-CHOP: '''<u>R</u>'''ituximab and hyaluronidase, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisolone
 
−
===Example orders===
 
−
*[[Example orders for R-CHOP in lymphoma]]
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:8a0576|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664395/ Lugtenburg et al. 2017 (MabEase)]
 
−
|2012-NR
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|[[#R-CHOP|R-CHOP]]
 
−
| style="background-color:#d9ef8b" |Might have superior CR rate
 
−
|-
 
−
|}
 
−
''Note: the details for CHOP are not available in the manuscript or supplement; we have reproduced common CHOP dosing, here. For patients achieving CR after cycle 4, the CHOP could be omitted after cycle 6.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Rituximab and hyaluronidase human (Rituxan Hycela)]] as follows:
 
−
**Cycles 2 to 8: 1400 mg SC once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
'''21-day cycle for 6 to 8 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''MabEase:''' Lugtenburg P, Avivi I, Berenschot H, Ilhan O, Marolleau JP, Nagler A, Rueda A, Tani M, Turgut M, Osborne S, Smith R, Pfreundschuh M. Efficacy and safety of subcutaneous and intravenous rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in first-line diffuse large B-cell lymphoma: the randomized MabEase study. Haematologica. 2017 Nov;102(11):1913-1922. Epub 2017 Sep 21. [http://www.haematologica.org/content/102/11/1913 link to original article] '''contains partial protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664395/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28935843 PubMed] NCT01649856
 
−
==R-CHOP-14 {{#subobject:fc3bde|Regimen=1}}==
 
−
R-CHOP-14: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone every '''<u>14</u>''' days
 
−
===Synopsis===
 
−
To be completed. Note that most of the variation below is in the steroid dose.
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, prednisone 40 mg/m<sup>2</sup>, 4 to 6 cycles {{#subobject:6ec36f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5757680/ Lamy et al. 2017 (LYSA/GOELAMS 02-03)]
 
−
|2005-2014
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
'''14-day cycle for 4 to 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[Diffuse_large_B-cell_lymphoma_-_null_regimens#Observation|Observation]] versus [[#Radiation_therapy|IFRT]] x 40 Gy
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, prednisone 40 mg/m<sup>2</sup>, 8 cycles {{#subobject:6ec36f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(13)70122-0 Delarue et al. 2013 (LNH03-6B)]
 
−
|2003-2008
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#R-CHOP|R-CHOP21]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 
−
|-
 
−
|[https://doi.org/10.1182/blood.2020008750 Le Gouill et al. 2021 (GAINED)]
 
−
|2012-2015
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#G-CHOP_99|G-CHOP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS24
 
−
|-
 
−
|}
 
−
''Note: treatment in GAINED was PET-adapted; see paper for details.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
====Supportive therapy====
 
−
*ONE of the following, "according to the treating doctor's decision, fulfilling existing guidelines and product labelling at that time."
 
−
**[[Filgrastim (Neupogen)|Granulocyte colony-stimulating factor]]
 
−
**[[Pegfilgrastim (Neulasta)|Pegylated G-CSF]]
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] as follows:
 
−
**Cycles 1 to 4: 15 mg IT once on day 1
 
−
'''14-day cycle for 8 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, prednisone 100 mg, BSA-based vincristine, standard-dose IV rituximab {{#subobject:9cab31|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2016.67.2980 Cortelazzo et al. 2016]
 
−
|2005-2011
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|R-HDS
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS36
 
−
|
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1016/S1470-2045(17)30444-8 Chiappella et al. 2017 (DLCL04)]
 
−
|rowspan=2|2006-2010
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#R-MegaCHOP-14|R-MegaCHOP-14]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|
 
−
|-
 
−
|2. [[#R-CHOP-14|R-CHOP-14]], then [[#R-MAD_99|R-MAD]], then [[#BEAM.2C_then_auto_HSCT_99|BEAM, then auto HSCT]]<br> 3. [[#R-MegaCHOP-14|R-MegaCHOP-14]], then [[#R-MAD_99|R-MAD]], then [[#BEAM.2C_then_auto_HSCT_99|BEAM, then auto HSCT]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of FFS24
 
−
|
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116833/ Seymour et al. 2014 (MAIN)]
 
−
|2007-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#RA-CHOP-14_99|RA-CHOP-14]]
 
−
| style="background-color:#ffffbf" |Did not meet secondary endpoint of PFS
 
−
| style="background-color:#1a9850" |Better cardiac safety
 
−
|-
 
−
|[https://doi.org/10.1200/jco.19.03418 Lugtenburg et al. 2020 (HOVON-84)]
 
−
|2007-2012
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#RR-CHOP-14_99|RR-CHOP-14]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of CR rate
 
−
| style="background-color:#1a9850" |Less neutropenia and infections
 
−
|-
 
−
|}
 
−
''Note: in MAIN, CHOP-14 was given for 6 cycles and rituximab for 8 cycles. In Cortelazzo et al. 2016, there is no cap on the vincristine dose, and there is also a discrepancy between the prednisone dose in the body of the manuscript and that in the appendix Figure A1; these discrepancies were clarified by the corresponding author in January 2017. In the abstract of DLCL04, there is no cap on vincristine.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
====Supportive therapy====
 
−
*ONE of the following:
 
−
**[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on days 7 to 11
 
−
**[[Pegfilgrastim (Neulasta)]]
 
−
'''14-day cycle for 6 to 8 cycles (see note)'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #4, prednisone 100 mg, BSA-based vincristine, high-dose IV rituximab {{#subobject:5fb2fa|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://meetinglibrary.asco.org/content/133133-144 Pfreundschuh et al. 2014 (SEXIE-R-CHOP-14)]
 
−
|NR in abstract
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 
−
|See below
 
−
|TBD
 
−
|-
 
−
|}
 
−
''Note: two arms were assessed; results are pending from this comparison. These higher doses were for males, only.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] by ONE of the following schedules:
 
−
**Cycles 1 to 8: 500 mg/m<sup>2</sup> IV once on day 1
 
−
**500 mg/m<sup>2</sup> IV once per day on days -1, 0, 3, 7, 14, 21, 28, 42
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
'''14-day cycle for 6 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #5, prednisone 100 mg, flat dose vincristine, 2 cycles, with response adaptation {{#subobject:a01893|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2017.76.8093 Dührsen et al. 2018 (PETAL)]
 
−
|2007-2012
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase III RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Vincristine_.26_Prednisone|Vincristine & prednisone]] pre-phase
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 2
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 2
 
−
*[[Vincristine (Oncovin)]] 2 mg IV once on day 2
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 2 to 6
 
−
'''14-day cycle for 2 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*PET-negative: [[#R-CHOP|R-CHOP]] x 4 (6 cycles total) versus [[#R-CHOP|R-CHOP]] x 4, then [[#Rituximab_monotherapy|rituximab]] x 2
 
−
*PET-positive: [[#R-CHOP|R-CHOP]] x 6 (8 cycles total) versus [[Regimen_classes#Intensive_chemotherapy|intensive Burkitt lymphoma protocol]]
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #6, prednisone 100 mg, flat dose vincristine, 6 cycles, extended rituximab exposure {{#subobject:aae4db|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2013.54.6861 Pfreundschuh et al. 2014 (SMARTE-R-CHOP-14)]
 
−
|2007-2009
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Vincristine_.26_Prednisone|Vincristine & prednisone]] pre-phase
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days -4, 0, 10, 29, 57, 99, 155, 239 (independent of CHOP cycles)
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
====Supportive therapy====
 
−
*ONE of the following starting on day 4, to continue until count recovery:
 
−
**[[Filgrastim (Neupogen)]]
 
−
**[[Lenograstim (Granocyte)]]
 
−
'''14-day cycle for 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients with initial bulky disease ("lymphoma masses or conglomerates with a diameter greater than or equal to 7.5 cm) or extranodal involvement"): [[#Radiation_therapy|RT]] x 36 Gy
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #7, prednisone 100 mg, flat dose vincristine, 6-8 cycles {{#subobject:30c25c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
| rowspan="3" |[https://doi.org/10.1016/S1470-2045%2808%2970002-0 Pfreundschuh et al. 2008 (RICOVER-60)]
 
−
|rowspan=3|2000-2005
 
−
| rowspan="3" style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP-14|CHOP-14]] x 6
 
−
| style="background-color:#1a9850" |Superior OS
 
−
|-
 
−
|2. [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP-14|CHOP-14]] x 8
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|3. [[#R-CHOP-14|R-CHOP-14]] x 8
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2013.51.4505 Held et al. 2014 (RICOVER-noRTh)]
 
−
|2005-2007
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*RICOVER-60: [[#Vincristine_.26_Prednisone|Vincristine & prednisone]] pre-phase
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
====Supportive therapy====
 
−
*ONE of the following starting on day 4, to continue until count recovery:
 
−
**[[Filgrastim (Neupogen)]]
 
−
**[[Lenograstim (Granocyte)]]
 
−
'''14-day cycle for 6 to 8 cycles (8 doses of rituximab regardless of total number of cycles)'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*RICOVER-60: Patients with initial bulky disease ("lymphoma masses or conglomerates with a diameter greater than or equal to 7.5 cm) or extranodal involvement"): [[#Radiation_therapy|RT]] x 36 Gy
 
−
*RICOVER-noRTh: [[#Radiation_therapy|RT]] x 36 Gy versus [[Diffuse_large_B-cell_lymphoma_-_null_regimens#Observation|observation]]
 
−
</div></div>
 
−
===References===
 
−
#'''RICOVER-60:''' Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, Reiser M, Nickenig C, Clemens M, Peter N, Bokemeyer C, Eimermacher H, Ho A, Hoffmann M, Mertelsmann R, Trümper L, Balleisen L, Liersch R, Metzner B, Hartmann F, Glass B, Poeschel V, Schmitz N, Ruebe C, Feller AC, Loeffler M; German High-Grade Non-Hodgkin Lymphoma Study Group. Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol. 2008 Feb;9(2):105-16. [https://doi.org/10.1016/S1470-2045%2808%2970002-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18226581 PubMed] NCT00052936
 
−
#'''Abstract:''' S. Le Gouill, N. J. Milpied, T. Lamy, V. Delwail, R. Gressin, D. Guyotat, G. L. Damaj, C. Foussard, G. Cartron, H. Maisonneuve, E. Deconinck, F. Dreyfus, E. Gyan, L. Sutton, N. Morineau, M. Alexis, F. Perry, M. Sauvezie. First-line rituximab (R) high-dose therapy (R-HDT) versus R-CHOP14 for young adults with diffuse large B-cell lymphoma: Preliminary results of the GOELAMS 075 prospective multicenter randomized trial. Journal of Clinical Oncology 29, no. 15_suppl (May 2011) 8003-8003. [https://doi.org/10.1200/jco.2011.29.15_suppl.8003 link to abstract]
 
−
#'''LNH03-6B:''' Delarue R, Tilly H, Mounier N, Petrella T, Salles G, Thieblemont C, Bologna S, Ghesquières H, Hacini M, Fruchart C, Ysebaert L, Fermé C, Casasnovas O, Van Hoof A, Thyss A, Delmer A, Fitoussi O, Molina TJ, Haioun C, Bosly A. Dose-dense rituximab-CHOP compared with standard rituximab-CHOP in elderly patients with diffuse large B-cell lymphoma (the LNH03-6B study): a randomised phase 3 trial. Lancet Oncol. 2013 May;14(6):525-33. Epub 2013 Apr 9. [https://doi.org/10.1016/S1470-2045(13)70122-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23578722 PubMed] NCT00144755
 
−
#'''RICOVER-noRTh:''' Held G, Murawski N, Ziepert M, Fleckenstein J, Pöschel V, Zwick C, Bittenbring J, Hänel M, Wilhelm S, Schubert J, Schmitz N, Löffler M, Rübe C, Pfreundschuh M. Role of radiotherapy to bulky disease in elderly patients with aggressive B-cell lymphoma. J Clin Oncol. 2014 Apr 10;32(11):1112-8. Epub 2014 Feb 3. [https://doi.org/10.1200/JCO.2013.51.4505 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24493716 PubMed] NCT00052936
 
−
#'''Abstract:''' Michael Pfreundschuh, Gerhard Held, Samira Zeynalova, Carsten Zwick, Mathias Haenel, Lorenz Truemper, Martin H. Dreyling, Judith Dierlamm, Markus Loeffler, Norbert Schmitz, Niels Murawski, German High-Grade Non-Hodgkin Lymphoma Study Group. Increased rituximab (R) doses and effect on risk of elderly male patients with aggressive CD20+ B-cell lymphomas: Results from the SEXIE-R-CHOP-14 trial of the DSHNHL. J Clin Oncol 32:5s, 2014 (suppl; abstr 8501) [http://meetinglibrary.asco.org/content/133133-144 link to original abstract] NCT00290667
 
−
#'''MAIN:''' Seymour JF, Pfreundschuh M, Trnený M, Sehn LH, Catalano J, Csinady E, Moore N, Coiffier B; MAIN Study Investigators. R-CHOP with or without bevacizumab in patients with previously untreated diffuse large B-cell lymphoma: final MAIN study outcomes. Haematologica. 2014 Aug;99(8):1343-9. Epub 2014 Jun 3. [http://www.haematologica.org/content/99/8/1343.abstract link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116833/ link to PMC article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/24895339 PubMed] NCT00486759
 
−
#'''SMARTE-R-CHOP-14:''' Pfreundschuh M, Poeschel V, Zeynalova S, Hänel M, Held G, Schmitz N, Viardot A, Dreyling MH, Hallek M, Mueller C, Wiesen MH, Witzens-Harig M, Truemper L, Keller U, Rixecker T, Zwick C, Murawski N; German High-Grade Non-Hodgkin Lymphoma Study Group. Optimization of rituximab for the treatment of diffuse large B-cell lymphoma (II): extended rituximab exposure time in the SMARTE-R-CHOP-14 trial of the German High-Grade Non-Hodgkin Lymphoma Study Group. J Clin Oncol. 2014 Dec 20;32(36):4127-33. Epub 2014 Nov 17. Erratum in: J Clin Oncol. 2015 Jun 10;33(17):1991. [https://doi.org/10.1200/jco.2013.54.6861 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25403207 PubMed] NCT00052936
 
−
<!-- Presented in part at the 54th American Society of Hematology Annual Meeting, Atlanta, GA, December 8-11, 2012, and the 12th International Conference on Malignant Lymphoma, Lugano, Switzerland, June 19-22, 2013 -->
 
−
#Cortelazzo S, Tarella C, Gianni AM, Ladetto M, Barbui AM, Rossi A, Gritti G, Corradini P, Di Nicola M, Patti C, Mulé A, Zanni M, Zoli V, Billio A, Piccin A, Negri G, Castellino C, Di Raimondo F, Ferreri AJ, Benedetti F, La Nasa G, Gini G, Trentin L, Frezzato M, Flenghi L, Falorio S, Chilosi M, Bruna R, Tabanelli V, Pileri S, Masciulli A, Delaini F, Boschini C, Rambaldi A. Randomized trial comparing R-CHOP versus high-dose sequential chemotherapy in high-risk patients with diffuse large B-cell lymphomas. J Clin Oncol. 2016 Nov 20;34(33):4015-4022. Epub 2016 Oct 31. [https://doi.org/10.1200/JCO.2016.67.2980 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28199143 PubMed] NCT00355199
 
−
#'''DLCL04:''' Chiappella A, Martelli M, Angelucci E, Brusamolino E, Evangelista A, Carella AM, Stelitano C, Rossi G, Balzarotti M, Merli F, Gaidano G, Pavone V, Rigacci L, Zaja F, D'Arco A, Cascavilla N, Russo E, Castellino A, Gotti M, Congiu AG, Cabras MG, Tucci A, Agostinelli C, Ciccone G, Pileri SA, Vitolo U. Rituximab-dose-dense chemotherapy with or without high-dose chemotherapy plus autologous stem-cell transplantation in high-risk diffuse large B-cell lymphoma (DLCL04): final results of a multicentre, open-label, randomised, controlled, phase 3 study. Lancet Oncol. 2017 Aug;18(8):1076-1088. Epub 2017 Jun 28. [https://doi.org/10.1016/S1470-2045(17)30444-8 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28668386 PubMed] NCT00499018
 
−
#'''MabEase:''' Lugtenburg P, Avivi I, Berenschot H, Ilhan O, Marolleau JP, Nagler A, Rueda A, Tani M, Turgut M, Osborne S, Smith R, Pfreundschuh M. Efficacy and safety of subcutaneous and intravenous rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in first-line diffuse large B-cell lymphoma: the randomized MabEase study. Haematologica. 2017 Nov;102(11):1913-1922. Epub 2017 Sep 21. [http://www.haematologica.org/content/102/11/1913 link to original article] '''contains partial protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664395/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28935843 PubMed] NCT01649856
 
−
#'''LYSA/GOELAMS 02-03:''' Lamy T, Damaj G, Soubeyran P, Gyan E, Cartron G, Bouabdallah K, Gressin R, Cornillon J, Banos A, Le Du K, Benchalal M, Moles MP, Le Gouill S, Fleury J, Godmer P, Maisonneuve H, Deconinck E, Houot R, Laribi K, Marolleau JP, Tournilhac O, Branger B, Devillers A, Vuillez JP, Fest T, Colombat P, Costes V, Szablewski V, Béné MC, Delwail V; LYSA. R-CHOP 14 with or without radiotherapy in nonbulky limited-stage diffuse large B-cell lymphoma. Blood. 2018 Jan 11;131(2):174-181. Epub 2017 Oct 23. [http://www.bloodjournal.org/content/131/2/174.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5757680/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29061568 PubMed] NCT00841945
 
−
#'''PETAL:''' Dührsen U, Müller S, Hertenstein B, Thomssen H, Kotzerke J, Mesters R, Berdel WE, Franzius C, Kroschinsky F, Weckesser M, Kofahl-Krause D, Bengel FM, Dürig J, Matschke J, Schmitz C, Pöppel T, Ose C, Brinkmann M, La Rosée P, Freesmeyer M, Hertel A, Höffkes HG, Behringer D, Prange-Krex G, Wilop S, Krohn T, Holzinger J, Griesshammer M, Giagounidis A, Raghavachar A, Maschmeyer G, Brink I, Bernhard H, Haberkorn U, Gaska T, Kurch L, van Assema DME, Klapper W, Hoelzer D, Geworski L, Jöckel KH, Scherag A, Bockisch A, Rekowski J, Hüttmann A; PETAL Trial Investigators. Positron emission tomography-guided therapy of aggressive non-Hodgkin lymphomas (PETAL): a multicenter, randomized phase III trial. J Clin Oncol. 2018 Jul 10;36(20):2024-2034. Epub 2018 May 11. [https://doi.org/10.1200/JCO.2017.76.8093 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/29750632 PubMed] NCT00554164
 
−
#'''HOVON-84:''' Lugtenburg PJ, de Nully Brown P, van der Holt B, D'Amore FA, Koene HR, de Jongh E, Fijnheer R, van Esser JW, Böhmer LH, Pruijt JF, Verhoef GE, Hoogendoorn M, Bilgin MY, Nijland M, van der Burg-de Graauw NC, Oosterveld M, Jie KG, Larsen TS, van der Poel MW, Leijs MB, Silbermann MH, van Marwijk Kooy M, Beeker A, Kersten MJ, Doorduijn JK, Tick LW, Brouwer RE, Lam KH, Burggraaff CN, de Keizer B, Arens AI, de Jong D, Hoekstra OS, Zijlstra-Baalbergen JM. Rituximab-CHOP With Early Rituximab Intensification for Diffuse Large B-Cell Lymphoma: A Randomized Phase III Trial of the HOVON and the Nordic Lymphoma Group (HOVON-84). J Clin Oncol. 2020 Oct 10;38(29):3377-3387. Epub 2020 Jul 30. [https://doi.org/10.1200/jco.19.03418 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32730183 PubMed] EudraCT 2006-005174-42
 
−
#'''GAINED:''' Le Gouill S, Ghesquières H, Oberic L, Morschhauser F, Tilly H, Ribrag V, Lamy T, Thieblemont C, Maisonneuve H, Gressin R, Bouhabdallah K, Haioun C, Damaj G, Fornecker L, Bouhabdallah R, Feugier P, Sibon D, Cartron G, Bonnet C, André M, Chartier L, Ruminy P, Kraeber-Bodéré F, Bodet-Milin C, Berriolo-Riedinger A, Brière J, Jais JP, Molina TJ, Itti E, Casasnovas RO. Obinutuzumab vs rituximab for advanced DLBCL: a PET-guided and randomized phase 3 study by LYSA. Blood. 2021 Apr 29;137(17):2307-2320. [https://doi.org/10.1182/blood.2020008750 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/33211799/ PubMed] NCT01659099
 
−
==R-CHOP-14 (Prednisolone) {{#subobject:fc3zyb|Regimen=1}}==
 
−
R-CHOP-14: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisolone every '''<u>14</u>''' days
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1 {{#subobject:81ghb1|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1002/hon.2524 Hara et al. 2018]
 
−
|2006-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#R-THP-CHOP_88|R-THP-CHOP]]
 
−
| style="background-color:#eeee01" |Non-inferior CR rate
 
−
|-
 
−
|}
 
−
''Note: large portions of the protocol, including the total number of cycles, are in Japanese.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 3
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 3
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once on day 3
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisolone (Millipred)]] 100 mg PO once per day on days 3 to 7
 
−
====Supportive therapy====
 
−
*[[Filgrastim (Neupogen)]] 50 mcg/kg SC once per day on days 9 to 14
 
−
'''14-day cycle for 6 cycles (see note)'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2 {{#subobject:8136b1|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(13)60313-X Cunningham et al. 2013 (UK NCRI R-CHOP14v21)]
 
−
|2005-2008
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#R-CHOP_.28Prednisolone.29|R-CHOP-21]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>OS24: 83% vs 81%<br>(HR 0.90, 95% CI 0.70-1.15)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 1 to 6: 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] as follows:
 
−
**Cycles 1 to 6: 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] as follows:
 
−
**Cycles 1 to 6: 2 mg IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisolone (Millipred)]] as follows:
 
−
**Cycles 1 to 6: 100 mg PO once per day on days 1 to 5
 
−
====CNS therapy, prophylaxis====
 
−
Per investigator discretion, but Cunningham et al. 2013 recommended that patients who had involvement of the "bone marrow, peripheral blood, nasal or paranasal sinuses, orbit, and testis" (they probably intended to say "or testis") receive:
 
−
*[[Methotrexate (MTX)]] 12.5 mg IT "for the first three cycles of treatment, administered as per local guidelines." No other details given.
 
−
====Supportive therapy====
 
−
*[[Lenograstim (Granocyte)]] (dose/route not specified) given on days 4 to 12
 
−
*[[Allopurinol (Zyloprim)]] 300 mg PO once per day during cycle 1
 
−
*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|Co-trimoxazole]] 480 mg (route not specified) twice per day on 3 days per week, taken throughout therapy, ending 2 weeks after treatment is completed
 
−
'''14-day cycle for 8 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''UK NCRI R-CHOP14v21:''' Cunningham D, Hawkes EA, Jack A, Qian W, Smith P, Mouncey P, Pocock C, Ardeshna KM, Radford JA, McMillan A, Davies J, Turner D, Kruger A, Johnson P, Gambell J, Linch D. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles. Lancet. 2013 May 25;381(9880):1817-26. Epub 2013 Apr 22. [https://doi.org/10.1016/S0140-6736(13)60313-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23615461 PubMed] ISRCTN16017947
 
−
#Hara T, Yoshikawa T, Goto H, Sawada M, Yamada T, Fukuno K, Kasahara S, Shibata Y, Matsumoto T, Mabuchi R, Nakamura N, Nakamura H, Ninomiya S, Kitagawa J, Kanemura N, Nannya Y, Katsumura N, Takahashi T, Kito Y, Takami T, Miyazaki T, Takeuchi T, Shimizu M, Tsurumi H. R-THP-COP versus R-CHOP in patients younger than 70 years with untreated diffuse large B cell lymphoma: A randomized, open-label, noninferiority phase 3 trial. Hematol Oncol. 2018 Oct;36(4):638-644. Epub 2018 Jun 8. [https://doi.org/10.1002/hon.2524 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/29882279 PubMed] UMIN000007283
 
−
==R-CHOP-14 (Rituximab and hyaluronidase) {{#subobject:fcbace|Regimen=1}}==
 
−
R-CHOP-14: '''<u>R</u>'''ituximab and hyaluronidaase, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone every '''<u>14</u>''' days
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:dc3888|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664395/ Lugtenburg et al. 2017 (MabEase)]
 
−
|2012-NR
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 
−
|[[#R-CHOP-14|R-CHOP-14]]
 
−
| style="background-color:#d9ef8b" |Might have superior CR rate
 
−
|-
 
−
|}
 
−
''Note: the details for CHOP-14 are not available in the manuscript or supplement; we have reproduced common CHOP-14 dosing, here. For patients achieving CR after cycle 4, the CHOP-14 could be omitted after cycle 6.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Rituximab and hyaluronidase human (Rituxan Hycela)]] as follows:
 
−
**Cycles 2 to 8: 1400 mg SC once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
====Supportive therapy====
 
−
*ONE of the following:
 
−
**[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on days 7 to 11
 
−
**[[Pegfilgrastim (Neulasta)]]
 
−
'''14-day cycle for 6 to 8 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''MabEase:''' Lugtenburg P, Avivi I, Berenschot H, Ilhan O, Marolleau JP, Nagler A, Rueda A, Tani M, Turgut M, Osborne S, Smith R, Pfreundschuh M. Efficacy and safety of subcutaneous and intravenous rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in first-line diffuse large B-cell lymphoma: the randomized MabEase study. Haematologica. 2017 Nov;102(11):1913-1922. Epub 2017 Sep 21. [http://www.haematologica.org/content/102/11/1913 link to original article] '''contains partial protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664395/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28935843 PubMed] NCT01649856
 
−
==R2-CHOP {{#subobject:2a4e31|Regimen=1}}==
 
−
R2-CHOP: '''<u>R</u>'''ituximab, '''<u>R</u>'''evlimid (Lenalidomide), '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone
 
−
<br>LR-CHOP-21: '''<u>L</u>'''enalidomide, '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone given every '''<u>21</u>''' days
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, len 15 mg/day for 14 d/cycle, pred 40 mg/m<sup>2</sup> {{#subobject:6fc8a3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70191-3 Vitolo et al. 2014 (REAL07)]
 
−
|2008-2009
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#f7fcfd" |ORR: 92% (95% CI 81–97)
 
−
|-
 
−
|}
 
−
''Note: CNS prophylaxis was offered to "at risk" patients.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] 15 mg PO once per day on days 1 to 14
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] as follows:
 
−
**Cycles 1 to 4: 12 mg IT once on day 1
 
−
====Supportive therapy====
 
−
*[[:Category:Granulocyte_colony-stimulating_factors|Granulocyte colony-stimulating factors]] (dose/duration not specified)
 
−
*[[:Category:Low_molecular_weight_heparins|Low-molecular-weight heparins]] (dose/duration not specified)
 
−
*PCP prophylaxis with one of the following:
 
−
**[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] (dose/duration not specified)
 
−
**[[Pentamidine (Nebupent)]] (dose/duration not specified)
 
−
*Carriers of hepatitis B virus: [[Lamivudine (Epivir)]] (dose/duration not specified)
 
−
'''21-day cycle for 6 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, len 15 mg/day for 14 d/cycle, pred 100 mg {{#subobject:6fc103|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.20.01366 Nowakowski et al. 2021 (ROBUST)]
 
−
|2015-2017
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#R-CHOP|R-CHOP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS<br>Median PFS: NYR vs NYR<br>(HR 0.85, 95% CI 0.63-1.14)
 
−
|-
 
−
|}
 
−
''Note: patients were allowed to receive to additional doses of rituximab, per local practices.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Biomarker eligibility criteria====
 
−
*ABC subtype, per NanoString Lymphoma Subtyping Test
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] 15 mg PO once per day on days 1 to 14
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
'''21-day cycle for 6 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, len 25 mg/day for 10 d/cycle {{#subobject:ea91fc|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
! style="width: 33%" |Study
 
−
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2014.55.5714 Nowakowski et al. 2014 (Mayo Clinic MC078E)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#f7fcfd" |ORR: 98%
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 10
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
====Supportive therapy====
 
−
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 2
 
−
*[[Aspirin]] 81 mg PO once per day unless on therapeutic dose [[Warfarin (Coumadin)]] or [[:Category:Low_molecular_weight_heparins|low molecular weight heparin]]
 
−
'''21-day cycle for up to 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- # '''Phase 1:''' Chiappella A, Tucci A, Castellino A, Pavone V, Baldi I, Carella AM, Orsucci L, Zanni M, Salvi F, Liberati AM, Gaidano G, Bottelli C, Rossini B, Perticone S, De Masi P, Ladetto M, Ciccone G, Palumbo A, Rossi G, Vitolo U. Lenalidomide plus cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab is safe and effective in untreated elderly diffuse large B-cell lymphoma patients: phase I study by the Fondazione Italiana Linfomi. Haematologica. 2013 Nov;98(11):1732-8. Epub 2013 Jun 28. [http://www.haematologica.org/content/98/11/1732 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3815174/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23812930 PubMed] -->
 
−
<!-- # '''Abstract:''' Chiappella A et al. Rituximab-CHOP21 plus lenalidomide (LR-CHOP21) is effective and feasible in elderly untreated diffuse large B-cell lymphoma (DLBCL): Results of Phase II REAL07 study of the Fondazione Italiana Linfomi (FIL). Proc ASH 2012; [http://abstracts.hematologylibrary.org/cgi/content/abstract/120/21/903?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=abstract+903&searchid=1&FIRSTINDEX=0&volume=120&issue=21&resourcetype=HWCIT Abstract 903]. -->
 
−
#'''REAL07:''' Vitolo U, Chiappella A, Franceschetti S, Carella AM, Baldi I, Inghirami G, Spina M, Pavone V, Ladetto M, Liberati AM, Molinari AL, Zinzani P, Salvi F, Fattori PP, Zaccaria A, Dreyling M, Botto B, Castellino A, Congiu A, Gaudiano M, Zanni M, Ciccone G, Gaidano G, Rossi G; Fondazione Italiana Linfomi. Lenalidomide plus R-CHOP21 in elderly patients with untreated diffuse large B-cell lymphoma: results of the REAL07 open-label, multicentre, phase 2 trial. Lancet Oncol. 2014 Jun;15(7):730-7. Epub 2014 May 12. [https://doi.org/10.1016/S1470-2045(14)70191-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24831981 PubMed] NCT00907348
 
−
<!--# '''Abstract:''' Nowakowski GS et al. Combination of lenalidomide with R-CHOP (R2CHOP) is well-tolerated and effective as initial therapy for aggressive B-cell lymphomas — A Phase II study. Proc ASH 2012; [http://abstracts.hematologylibrary.org/cgi/content/abstract/120/21/689?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=abstract+689&searchid=1&FIRSTINDEX=0&volume=120&issue=21&resourcetype=HWCIT Abstract 689].
 
−
# '''Abstract:''' Grzegorz S. Nowakowski, Betsy LaPlant, William R Macon, Craig B. Reeder, James M. Foran, Garth D. Nelson, Carrie A. Thompson, Candido Rivera, David James Inwards, Ivana N. M. Micallef, Patrick B. Johnston, Luis F. Porrata, Stephen Maxted Ansell, Thomas Matthew Habermann, Thomas E. Witzig. Effect of lenalidomide combined with R-CHOP (R2CHOP) on negative prognostic impact of nongerminal center (non-GCB) phenotype in newly diagnosed diffuse large B-cell lymphoma: A phase 2 study. J Clin Oncol 32:5s, 2014 (suppl; abstr 8520) [http://meetinglibrary.asco.org/content/134031-144 link to original abstract] -->
 
−
#'''Mayo Clinic MC078E:''' Nowakowski GS, LaPlant B, Macon WR, Reeder CB, Foran JM, Nelson GD, Thompson CA, Rivera CE, Inwards DJ, Micallef IN, Johnston PB, Porrata LF, Ansell SM, Gascoyne RD, Habermann TM, Witzig TE. Lenalidomide combined with R-CHOP overcomes negative prognostic impact of non-germinal center B-cell phenotype in newly diagnosed diffuse large B-cell lymphoma: a phase II study. J Clin Oncol. 2015 Jan 20;33(3):251-7. Epub 2014 Aug 18. [https://doi.org/10.1200/jco.2014.55.5714 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25135992 PubMed] NCT00670358
 
−
#'''ROBUST:''' Nowakowski GS, Chiappella A, Gascoyne RD, Scott DW, Zhang Q, Jurczak W, Özcan M, Hong X, Zhu J, Jin J, Belada D, Bergua JM, Piazza F, Mócikova H, Molinari AL, Yoon DH, Cavallo F, Tani M, Yamamoto K, Izutsu K, Kato K, Czuczman M, Hersey S, Kilcoyne A, Russo J, Hudak K, Zhang J, Wade S, Witzig TE, Vitolo U. ROBUST: A Phase III Study of Lenalidomide Plus R-CHOP Versus Placebo Plus R-CHOP in Previously Untreated Patients With ABC-Type Diffuse Large B-Cell Lymphoma. J Clin Oncol. 2021 Apr 20;39(12):1317-1328. Epub 2021 Feb 23. [https://doi.org/10.1200/jco.20.01366 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33621109/ PubMed] NCT02285062
 
−
==DA-R-EPOCH {{#subobject:ba36e5|Regimen=1}}==
 
−
DA-R-EPOCH: '''<u>D</u>'''ose '''<u>A</u>'''djusted '''<u>R</u>'''ituximab, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>O</u>'''ncovin (Vincristine), '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin)
 
−
<br>DA-EPOCH-R
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:6c5478|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 17%"|Study
 
−
!style="width: 15%"|Years of enrollment
 
−
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 17%"|Comparator
 
−
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409217/ Wilson et al. 2008]
 
−
|NR
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342980/ Wilson et al. 2011 (CALGB 50103)]
 
−
|2002-2004
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1111/j.1365-2141.2006.06438.x García-Suárez et al. 2007]
 
−
|2002-2006
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.13273 Purroy et al. 2014]
 
−
|2002-2008
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6774813/ Bartlett et al. 2019 (CALGB 50303)]
 
−
|2005-2013
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#R-CHOP|R-CHOP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS<br>PFS24: 79% vs 75.5%<br>(HR 0.93, 95% CI 0.68-1.27)
 
−
| style="background-color:#d73027" |Increased toxicity
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per cycle on day -1 or 1, '''given before the start of EPOCH''' (depending on reference)
 
−
====Chemotherapy====
 
−
*[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 200 mg/m<sup>2</sup>)
 
−
*[[Vincristine (Oncovin)]] 0.4 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1.6 mg/m<sup>2</sup>)
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV over 15 minutes once on day 5
 
−
*[[Doxorubicin (Adriamycin)]] 10 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m<sup>2</sup>)
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO twice per day on days 1 to 5
 
−
====Supportive therapy====
 
−
*Growth factor support with one of the following:
 
−
**[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 6 and continuing until ANC greater than 5000/uL past nadir
 
−
**[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 6 (option per Purroy et al. 2014)
 
−
*PCP prophylaxis with any one of the following:
 
−
**[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] 160/800 mg PO twice per day 3 days per week
 
−
***Alternative used only in García-Suárez et al. 2007: cotrimoxazole 480 mg PO twice per day 3 days per week
 
−
**[[Atovaquone (Mepron)]] 1500 mg PO once per day
 
−
**[[Pentamidine (Nebupent)]] 300 mg nebulized every 28 days
 
−
*Only in García-Suárez et al. 2007: [[Darbepoetin alfa (Aranesp)]] 2.25 mcg/kg SC when hemoglobin concentration was less than or equal to 10 g/dL.
 
−
'''21-day cycle for 6 to 8 cycles'''
 
−
====Dose modifications====
 
−
*Start cycle 1 as described above.
 
−
*Obtain CBCs twice per week for nadir measurements.
 
−
*If nadir ANC greater than 500/uL, increase etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
 
−
*If nadir ANC less than 500/uL on 1 or 2 measurements, use same doses as last cycle.
 
−
*If nadir ANC less than 500/uL on at least 3 measurements, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
 
−
*And/or if nadir platelet count less than 25 × 10<sup>9</sup>/L on at least 1 measurement, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
 
−
*'''Dose adjustments below the cycle 1 starting dose only applies to cyclophosphamide.''' The lowest etoposide and doxorubicin would be dosed at is the original cycle 1 dose.
 
−
*Can start new cycle every 21 days if ANC greater than 1000/uL and platelets greater than 100 × 10<sup>9</sup>/L. If counts are below those levels, check daily CBC and continue growth factor support until counts are adequate and next cycle can start.
 
−
</div></div>
 
−
===References===
 
−
#García-Suárez J, Bañas H, Arribas I, De Miguel D, Pascual T, Burgaleta C. Dose-adjusted EPOCH plus rituximab is an effective regimen in patients with poor-prognostic untreated diffuse large B-cell lymphoma: results from a prospective observational study. Br J Haematol. 2007 Jan;136(2):276-85. [https://doi.org/10.1111/j.1365-2141.2006.06438.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17233819 PubMed]
 
−
#Wilson WH, Dunleavy K, Pittaluga S, Hegde U, Grant N, Steinberg SM, Raffeld M, Gutierrez M, Chabner BA, Staudt L, Jaffe ES, Janik JE. Phase II study of dose-adjusted EPOCH and rituximab in untreated diffuse large B-cell lymphoma with analysis of germinal center and post-germinal center biomarkers. J Clin Oncol. 2008 Jun 1;26(16):2717-24. [https://doi.org/10.1200/jco.2007.13.1391 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409217/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18378569 PubMed]
 
−
#'''CALGB 50103:''' Wilson WH, Jung SH, Porcu P, Hurd D, Johnson J, Martin SE, Czuczman M, Lai R, Said J, Chadburn A, Jones D, Dunleavy K, Canellos G, Zelenetz AD, Cheson BD, Hsi ED; Cancer and Leukemia Group B. A Cancer and Leukemia Group B multi-center study of DA-EPOCH-rituximab in untreated diffuse large B-cell lymphoma with analysis of outcome by molecular subtype. Haematologica. 2012 May;97(5):758-65. Epub 2011 Dec 1. [http://www.haematologica.org/content/97/5/758.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342980/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22133772 PubMed] NCT00032019
 
−
<!-- previously presented in part at the 51st Annual Meeting of the American Society of Hematology, New Orleans, LA, December 5-8, 2009, and the 53rd Annual Meeting of the American Society of Hematology, San Diego, CA, December 10-13, 2011. -->
 
−
#Purroy N, Bergua J, Gallur L, Prieto J, Lopez LA, Sancho JM, García-Marco JA, Castellví J, Montes-Moreno S, Batlle A, de Villambrosia SG, Carnicero F, Ferrando-Lamana L, Piris MA, Lopez A; PETHEMA. Long-term follow-up of dose-adjusted EPOCH plus rituximab (DA-EPOCH-R) in untreated patients with poor prognosis large B-cell lymphoma: a phase II study conducted by the Spanish PETHEMA group. Br J Haematol. 2015 Apr;169(2):188-98. Epub 2014 Dec 18. [https://doi.org/10.1111/bjh.13273 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25521006 PubMed] EudraCT 2004-001684-22
 
−
<!-- Prior publication: Poster presentation at the 2014 annual meeting of the American Society of Hematology (Howlett C, Landsburg DJ, Chong EA, Snedecor SJ, Schuster SJ, Green TM, Cohen JB, Svoboda J, Nasta SD, Feldman T, Rago R, Land D, Walsh KM, Goy A, Mato AR. Front-line, dose-escalated immunochemotherapy is associated with a significant PFS (but not OS) advantage in 401 patients (pts) with double-hit lymphomas (DHL): A systematic review and meta-analysis. Blood, 124, abst 3056). -->
 
−
#'''Retrospective:''' Howlett C, Snedecor SJ, Landsburg DJ, Svoboda J, Chong EA, Schuster SJ, Nasta SD, Feldman T, Rago A, Walsh KM, Weber S, Goy A, Mato A. Front-line, dose-escalated immunochemotherapy is associated with a significant progression-free survival advantage in patients with double-hit lymphomas: a systematic review and meta-analysis. Br J Haematol. 2015 Aug;170(4):504-14. Epub 2015 Apr 24. [https://doi.org/10.1111/bjh.13463 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25907897 PubMed]
 
−
<!-- # '''Abstract:''' Wyndham H. Wilson, MD, PhD, Jung sin-Ho, Brandelyn Nicole Pitcher, MS, Eric D Hsi, MD, Jonathan Friedberg, MD, Bruce Cheson, MD, Nancy L Bartlett, MD, Scott Smith, Nina Wagner Johnston, MD, Brad S Kahl, Louis M. Staudt, MD, PhD, Kristie Blum, MD, Jeremy Abramson, Oliver W Press, MD, PhD, Richard I. Fisher, MD, Kristy L. Richards, PhD, MD, Heiko Schoder, MD, Julie E Chang, Andrew D. Zelenetz and John P. Leonard, MD. Phase III Randomized Study of R-CHOP Versus DA-EPOCH-R and Molecular Analysis of Untreated Diffuse Large B-Cell Lymphoma: CALGB/Alliance 50303. ASH 2016 Abstract 469 [https://ashpublications.org/blood/article/128/22/469/101297/Phase-III-Randomized-Study-of-R-CHOP-Versus-DA link to abstract] -->
 
−
#'''CALGB 50303:''' Bartlett NL, Wilson WH, Jung SH, Hsi ED, Maurer MJ, Pederson LD, Polley MC, Pitcher BN, Cheson BD, Kahl BS, Friedberg JW, Staudt LM, Wagner-Johnston ND, Blum KA, Abramson JS, Reddy NM, Winter JN, Chang JE, Gopal AK, Chadburn A, Mathew S, Fisher RI, Richards KL, Schöder H, Zelenetz AD, Leonard JP. Dose-Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303. J Clin Oncol. 2019 Jul 20;37(21):1790-1799. Epub 2019 Apr 2. [https://doi.org/10.1200/JCO.18.01994 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6774813/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30939090 PubMed] NCT00118209
 
−
==R-Hyper-CVAD/R-MA {{#subobject:432427|Regimen=1}}==
 
−
R-Hyper-CVAD/R-MA: '''<u>R</u>'''ituximab, '''<u>Hyper</u>'''fractionated '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''incristine, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>D</u>'''examethasone alternating with '''<u>R</u>'''ituximab, '''<u>M</u>'''ethotrexate, '''<u>A</u>'''ra-C (Cytarabine)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol {{#subobject:b7ff27|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5278952/ Oki et al. 2013 (MDACC 2005-0054)]
 
−
|2005-NR
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 
−
|[[#R-CHOP|R-CHOP]]
 
−
| style="background-color:#91cf60" |Seems to have increased CRR
 
−
|-
 
−
|}
 
−
''Intended for high-risk DLBCL (IPI greater than or equal to 3). The authors report "excellent outcome" in patients less than or equal to 45 years old, however patients greater than 45 years old had "unacceptable mortality."''
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy, Part A (cycles 1, 3, 5)====
 
−
*[[Cyclophosphamide (Cytoxan)]] 300 mg/m<sup>2</sup> IV every 12 hours on days 1 to 3 (total dose per cycle: 1800 mg/m<sup>2</sup>)
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 5 & 12
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 5
 
−
====Glucocorticoid therapy, Part A (cycles 1, 3, 5)====
 
−
*[[Dexamethasone (Decadron)]] 40 mg IV or PO once per day on days 2 to 5
 
−
====Supportive therapy, Part A (cycles 1, 3, 5)====
 
−
*[[Mesna (Mesnex)]] 600 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 1 (total dose per cycle: 1800 mg/m<sup>2</sup>)
 
−
*[[Filgrastim (Neupogen)]] or [[Pegfilgrastim (Neulasta)]] starting 24 to 48 hours after completion of chemotherapy
 
−
*[[Ciprofloxacin (Cipro)]] 500 mg PO twice per day for 10 days after chemotherapy
 
−
*[[Fluconazole (Diflucan)]] 100 mg PO once per day for 10 days after chemotherapy
 
−
*[[Valacyclovir (Valtrex)]] 500 mg PO once per day for 10 days after chemotherapy
 
−
'''Next cycle to start once ANC is greater than or equal to 1000/uL and platelet count is greater than or equal to 100 × 10<sup>9</sup>/L.'''
 
−
====Chemotherapy, Part B (cycles 2, 4, 6)====
 
−
*[[Methotrexate (MTX)]] 200 mg/m<sup>2</sup> IV over 2 hours once on day 1, then 800 mg/m<sup>2</sup> IV over 22 hours (total dose per cycle: 1000 mg/m<sup>2</sup>)
 
−
*[[Cytarabine (Ara-C)]] 3000 mg/m<sup>2</sup> IV over 2 hours every 12 hours on days 3 & 4 (total dose per cycle: 12,000 mg/m<sup>2</sup>)
 
−
====Supportive therapy, Part B (cycles 2, 4, 6)====
 
−
*[[Folinic acid (Leucovorin)]] (dose/timing not specified) until serum methotrexate level less than 100 nmol/L
 
−
*[[Sodium bicarbonate]] 1300 mg PO twice per day until methotrexate level less than 100 nmol/L
 
−
*[[Filgrastim (Neupogen)]] or [[Pegfilgrastim (Neulasta)]] starting 24 to 48 hours after completion of chemotherapy
 
−
*[[Ciprofloxacin (Cipro)]] 500 mg PO twice per day for 10 days after chemotherapy
 
−
*[[Fluconazole (Diflucan)]] 100 mg PO once per day for 10 days after chemotherapy
 
−
*[[Valacyclovir (Valtrex)]] 500 mg PO once per day for 10 days after chemotherapy
 
−
'''21-day cycles'''
 
−
====CNS therapy, prophylaxis====
 
−
''"Recommended in patients with paraspinal disease, paranasal sinus disease, testicular disease, bone marrow disease, diffuse osseous disease or greater than or equal to 2 sites of extranodal disease. Actual administration of prophylactic intrathecal chemotherapy was at the treating physician's discretion."''
 
−
====Dose modifications, Part A (cycles 1, 3, 5)====
 
−
*[[Vincristine (Oncovin)]] reduced once by 50% for NCI common toxicity criteria Grade 2+ peripheral neuropathy, omitted if Grade 2+ peripheral neuropathy persists
 
−
*[[Doxorubicin (Adriamycin)]] and [[Cyclophosphamide (Cytoxan)]] reduced by 20% in subsequent A cycles if neutropenic fever occurs, grade 3/4 non-hematological toxicity, or ANC less than 750/uL or platelet count less than 75 × 10<sup>9</sup>/L on day 21
 
−
''Although the protocol does not specify, it is assumed that if these thresholds are not met by day 21, the next cycle will start with the dose reductions as specified.''
 
−
====Dose modifications, Part B (cycles 2, 4, 6)====
 
−
*[[Methotrexate (MTX)]] reduced by 25% in subsequent B cycles if neutropenic fever occurs, grade 3/4 non-hematological toxicity, or ANC less than 750/uL or platelet count less than 75 × 10<sup>9</sup>/L on day 21
 
−
*[[Cytarabine (Ara-C)]] reduced by 33% in subsequent B cycles if neutropenic fever occurs, grade 3/4 non-hematological toxicity, or ANC less than 750/uL or platelet count less than 75 × 10<sup>9</sup>/L on day 21
 
−
</div></div>
 
−
===References===
 
−
#'''MDACC 2005-0054:''' Oki Y, Westin JR, Vega F, Chuang H, Fowler N, Neelapu S, Hagemeister FB, McLaughlin P, Kwak LW, Romaguera JE, Fanale M, Younes A, Rodriguez MA, Orlowski RZ, Wang M, Ouzounian ST, Samaniego F, Fayad L. Prospective phase II study of rituximab with alternating cycles of hyper-CVAD and high-dose methotrexate with cytarabine for young patients with high-risk diffuse large B-cell lymphoma. Br J Haematol. 2013 Dec;163(5):611-20. Epub 2013 Oct 1. [https://doi.org/10.1111/bjh.12585 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5278952/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24117234 PubMed] NCT00290498
 
−
<!-- Prior publication: Poster presentation at the 2014 annual meeting of the American Society of Hematology (Howlett C, Landsburg DJ, Chong EA, Snedecor SJ, Schuster SJ, Green TM, Cohen JB, Svoboda J, Nasta SD, Feldman T, Rago R, Land D, Walsh KM, Goy A, Mato AR. Front-line, dose-escalated immunochemotherapy is associated with a significant PFS (but not OS) advantage in 401 patients (pts) with double-hit lymphomas (DHL): A systematic review and meta-analysis. Blood, 124, abst 3056). -->
 
−
#'''Retrospective:''' Howlett C, Snedecor SJ, Landsburg DJ, Svoboda J, Chong EA, Schuster SJ, Nasta SD, Feldman T, Rago A, Walsh KM, Weber S, Goy A, Mato A. Front-line, dose-escalated immunochemotherapy is associated with a significant progression-free survival advantage in patients with double-hit lymphomas: a systematic review and meta-analysis. Br J Haematol. 2015 Aug;170(4):504-14. Epub 2015 Apr 24. [https://doi.org/10.1111/bjh.13463 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25907897 PubMed]
 
−
==R-MegaCHOP-14 {{#subobject:8e9669|Regimen=1}}==
 
−
R-MegaCHOP-14: '''<u>R</u>'''ituximab, "Mega" (high-dose) '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''redniso(lo)ne every 14 days
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:6d7b6c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1016/S1470-2045(17)30444-8 Chiappella et al. 2017 (DLCL04)]
 
−
|rowspan=2|2006-2010
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#R-CHOP-14|R-CHOP-14]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|2. [[#R-CHOP-14|R-CHOP-14]], then [[#R-MAD_99|R-MAD]], then [[#BEAM.2C_then_auto_HSCT_99|BEAM, then auto HSCT]]<br> 3. [[#R-MegaCHOP-14|R-MegaCHOP-14]], then [[#R-MAD_99|R-MAD]], then [[#BEAM.2C_then_auto_HSCT_99|BEAM, then auto HSCT]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of FFS24
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 1200 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 70 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
'''14-day cycle for 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#Chiappella A, Martelli M, Angelucci E, Brusamolino E, Evangelista A, Carella AM, Stelitano C, Rossi G, Balzarotti M, Merli F, Gaidano G, Pavone V, Rigacci L, Zaja F, D'Arco A, Cascavilla N, Russo E, Castellino A, Gotti M, Congiu AG, Cabras MG, Tucci A, Agostinelli C, Ciccone G, Pileri SA, Vitolo U. Rituximab-dose-dense chemotherapy with or without high-dose chemotherapy plus autologous stem-cell transplantation in high-risk diffuse large B-cell lymphoma (DLCL04): final results of a multicentre, open-label, randomised, controlled, phase 3 study. Lancet Oncol. 2017 Aug;18(8):1076-1088. Epub 2017 Jun 28. [https://doi.org/10.1016/S1470-2045(17)30444-8 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28668386 PubMed] NCT00499018
 
−
==R-miniCHOP (Rituximab and hyaluronidase) {{#subobject:17byh3|Regimen=1}}==
 
−
R-miniCHOP: '''<u>R</u>'''ituximab and hyaluronidaase, reduced-dose ('''mini''') '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''redniso(lo)ne
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:9fd3ee|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.20.02666 Oberic et al. 2021 (SENIOR)]
 
−
|2014-2017
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#R2-miniCHOP_99|R2-miniCHOP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
''Note: this regimen was intended for patients 80 years or older.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Rituximab and hyaluronidase human (Rituxan Hycela)]] as follows:
 
−
**Cycles 2 to 6: 1400 mg SC once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 400 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1 mg IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
'''21-day cycle for 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''SENIOR:''' Oberic L, Peyrade F, Puyade M, Bonnet C, Dartigues-Cuillères P, Fabiani B, Ruminy P, Maisonneuve H, Abraham J, Thieblemont C, Feugier P, Salles G, Bijou F, Pica GM, Damaj G, Haioun C, Casasnovas RO, Farhat H, Le Calloch R, Waultier-Rascalou A, Malak S, Paget J, Gat E, Tilly H, Jardin F. Subcutaneous Rituximab-MiniCHOP Compared With Subcutaneous Rituximab-MiniCHOP Plus Lenalidomide in Diffuse Large B-Cell Lymphoma for Patients Age 80 Years or Older. J Clin Oncol. 2021 Apr 10;39(11):1203-1213. Epub 2021 Jan 14. [https://doi.org/10.1200/jco.20.02666 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33444079/ PubMed]
 
−
==R-miniCEOP {{#subobject:cd6200|Regimen=1}}==
 
−
R-miniCEOP: '''<u>R</u>'''ituximab, mini, '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''pirubicin, '''<u>O</u>'''?? (vinblastine), '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:41cd4b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.3109/10428194.2011.621565 Merli et al. 2012 (ANZINTER3)]
 
−
|2003-2006
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|[[#R-CHOP|R-CHOP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vinblastine (Velban)]] 5 mg/m<sup>2</sup> IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 50 mg/m<sup>2</sup> IV or PO once per day on days 1 to 5
 
−
====Supportive therapy====
 
−
*Prophylactic [[:Category:Granulocyte colony-stimulating factors|G-CSF]] used for persisting grade 4 neutropenia or febrile neutropenia.
 
−
*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|Cotrimoxazole]] (dose/route/schedule not specified) prophylaxis.
 
−
*Erythropoietin use was allowed for hemoglobin less than 11 g/dL.
 
−
'''21-day cycle for 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients with initial bulky disease and/or partially responding sites received [[#Radiation_therapy|radiothearpy]]
 
−
</div></div>
 
−
===References===
 
−
#'''ANZINTER3:''' Merli F, Luminari S, Rossi G, Mammi C, Marcheselli L, Tucci A, Ilariucci F, Chiappella A, Musso M, Di Rocco A, Stelitano C, Alvarez I, Baldini L, Mazza P, Salvi F, Arcari A, Fragasso A, Gobbi PG, Liberati AM, Federico M. Cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab versus epirubicin, cyclophosphamide, vinblastine, prednisone and rituximab for the initial treatment of elderly "fit" patients with diffuse large B-cell lymphoma: results from the ANZINTER3 trial of the Intergruppo Italiano Linfomi. Leuk Lymphoma. 2012 Apr;53(4):581-8. Epub 2011 Nov 15. [https://doi.org/10.3109/10428194.2011.621565 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21895543 PubMed] NCT01148446
 
−
=Untreated, non-randomized or retrospective data=
 
−
==Bendamustine & Rituximab (BR) {{#subobject:305d42|Regimen=1}}==
 
−
BR: '''<u>B</u>'''endamustine, '''<u>R</u>'''ituximab
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 90 mg/m<sup>2</sup> {{#subobject:da8206|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063684/ Park et al. 2016 (LCCC 1011)]
 
−
|2011-2013
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Note: this dosing was intended for patients with [[Performance_status#ECOG_performance_status_.28WHO.2FGOG.2FZubrod_score.29|ECOG PS]] = 3 at baseline.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Bendamustine]] 90 mg/m<sup>2</sup> IV once per day on days 1 & 2, '''given first on day 1'''
 
−
**Dose increased to 120 mg/m<sup>2</sup> if ECOG PS improved to less than or equal to 2 after 3 cycles
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1, '''given second'''
 
−
'''21-day cycle for up to 8 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 120 mg/m<sup>2</sup> {{#subobject:2f4cc2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063684/ Park et al. 2016 (LCCC 1011)]
 
−
|2011-2013
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Bendamustine]] 120 mg/m<sup>2</sup> IV once per day on days 1 & 2, '''given first on day 1'''
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1, '''given second'''
 
−
'''21-day cycle for up to 8 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''LCCC 1011:''' Park SI, Grover NS, Olajide O, Asch AS, Wall JG, Richards KL, Sobol AL, Deal AM, Ivanova A, Foster MC, Muss HB, Shea TC. A phase II trial of bendamustine in combination with rituximab in older patients with previously untreated diffuse large B-cell lymphoma. Br J Haematol. 2016 Oct;175(2):281-289. [https://doi.org/10.1111/bjh.14232 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063684/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27448091 PubMed] NCT01234467
 
−
==Helicobacter pylori eradication therapy {{#subobject:be3ef5|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, before 1996 {{#subobject:6a2469|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/119/21/4838.long Kuo et al. 2012]
 
−
| style="background-color:#ffffbe" |Retrospective
 
−
|-
 
−
|}
 
−
''Note: This regimen is intended for the treatment of gastric DLBCL only; H. pylori eradication would not be an appropriate treatment for systemic DLBCL.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Antibiotic therapy====
 
−
*[[Amoxicillin]] 500 mg PO every 6 hours
 
−
*[[Metronidazole (Flagyl)]] 250 mg PO every 6 hours
 
−
*One of the following:
 
−
**[[Bismuth subcitrate]] 120 mg PO every 6 hours
 
−
**[[Omeprazole (Prilosec)]] 20 mg PO twice per day
 
−
'''28-day course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, after 1996 {{#subobject:6a3969|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/119/21/4838.long Kuo et al. 2012]
 
−
| style="background-color:#ffffbe" |Retrospective
 
−
|-
 
−
|}
 
−
''Note: This regimen is intended for the treatment of gastric DLBCL only; H. pylori eradication would not be an appropriate treatment for systemic DLBCL.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Antibiotic therapy====
 
−
*[[Amoxicillin]] 500 mg PO every 6 hours
 
−
*[[Clarithromycin (Biaxin)]] 500 mg PO twice per day
 
−
*[[Omeprazole (Prilosec)]] 20 mg PO twice per day
 
−
'''14-day course'''
 
−
</div></div>
 
−
===References===
 
−
#'''Retrospective:''' Kuo SH, Yeh KH, Wu MS, Lin CW, Hsu PN, Wang HP, Chen LT, Cheng AL. Helicobacter pylori eradication therapy is effective in the treatment of early-stage H pylori-positive gastric diffuse large B-cell lymphomas. Blood. 2012 May 24;119(21):4838-44. Epub 2012 Mar 7. [http://www.bloodjournal.org/content/119/21/4838.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/22403257 PubMed]
 
−
==O-miniCHOP {{#subobject:652b56|Regimen=1}}==
 
−
O-miniCHOP: '''<u>O</u>'''fatumumab, reduced-dose ('''mini''') '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''redniso(lo)ne
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:6d1193|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/S2352-3026(16)30171-5 Peyrade et al. 2017 (LYSA LNH09-7B)]
 
−
|2010-2011
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Vincristine_.26_Prednisone|Vincristine & prednisone]] pre-phase
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Ofatumumab (Arzerra)]] 1000 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 400 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1 mg IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
====Supportive therapy====
 
−
*[[Acetaminophen (Tylenol)]] 1000 mg PO once on day 1, prior to [[Ofatumumab (Arzerra)]]
 
−
*[[Diphenhydramine (Benadryl)]] 50 mg (route not specified) once on day 1, prior to [[Ofatumumab (Arzerra)]]
 
−
'''21-day cycle for 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''LYSA LNH09-7B:''' Peyrade F, Bologna S, Delwail V, Emile JF, Pascal L, Fermé C, Schiano JM, Coiffier B, Corront B, Farhat H, Fruchart C, Ghesquieres H, Macro M, Tilly H, Choufi B, Delarue R, Fitoussi O, Gabarre J, Haioun C, Jardin F; LYSA. Combination of ofatumumab and reduced-dose CHOP for diffuse large B-cell lymphomas in patients aged 80 years or older: an open-label, multicentre, single-arm, phase 2 trial from the LYSA group. Lancet Haematol. 2017 Jan;4(1):e46-e55. [https://doi.org/10.1016/S2352-3026(16)30171-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28041583 PubMed] NCT01195714
 
−
==R-BL {{#subobject:fe578a|Regimen=1}}==
 
−
R-BL: '''<u>R</u>'''ituximab, '''<u>B</u>'''endamustine, '''<u>L</u>'''enalidomide
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:f063a7|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.14049 Hitz et al. 2016 (SAKK 38/08)]
 
−
|NR
 
−
| style="background-color:#91cf61" |Phase 2, <20 pts in subgroup
 
−
|ORR: 61% (95% CI 45-76%)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Lenalidomide (Revlimid)]] 10 mg PO once per day on days 1 to 21
 
−
====Chemotherapy====
 
−
*[[Bendamustine]] 70 mg/m<sup>2</sup> IV once per day on days 1 & 2
 
−
'''28-day cycle for 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''SAKK 38/08:''' Hitz F, Zucca E, Pabst T, Fischer N, Cairoli A, Samaras P, Caspar CB, Mach N, Krasniqi F, Schmidt A, Rothermundt C, Enoiu M, Eckhardt K, Berardi Vilei S, Rondeau S, Mey U. Rituximab, bendamustine and lenalidomide in patients with aggressive B-cell lymphoma not eligible for anthracycline-based therapy or intensive salvage chemotherapy - SAKK 38/08. Br J Haematol. 2016 Jul;174(2):255-63. Epub 2016 Mar 28. [https://doi.org/10.1111/bjh.14049 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27018242 PubMed] NCT00987493
 
−
==R-CDOP {{#subobject:bdf229|Regimen=1}}==
 
−
R-CDOP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>D</u>'''oxil (Pegylated liposomal doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone
 
−
<br>DRCOP: '''<u>D</u>'''oxil (Pegylated liposomal doxorubicin), '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1 {{#subobject:7a864b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(14)00411-X Oki et al. 2014 (MDACC 2004-0305)]
 
−
|2005-NR in abstract
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Pegylated liposomal doxorubicin (Doxil)]] 40 mg/m<sup>2</sup> (maximum dose of 90 mg) IV over 60 minutes once on day 1
 
−
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
====Supportive therapy====
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day from day 2 until ANC greater than 3000/μl
 
−
OR
 
−
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 2
 
−
====Dose modifications====
 
−
*Dose reduction level 1 (see paper for triggers):
 
−
**[[Pegylated liposomal doxorubicin (Doxil)]] reduced to 35 mg/m<sup>2</sup>
 
−
**[[Cyclophosphamide (Cytoxan)]] reduced to 600 mg/m<sup>2</sup>
 
−
*Dose reduction level 2 (see paper for triggers):
 
−
**[[Pegylated liposomal doxorubicin (Doxil)]] reduced to 30 mg/m<sup>2</sup>
 
−
**[[Cyclophosphamide (Cytoxan)]] reduced to 450 mg/m<sup>2</sup>
 
−
'''21-day cycle for 6 to 8 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2 {{#subobject:5fd9ca|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1080/10428190600799946 Zaja et al. 2006]
 
−
|NR in abstract
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Only the dose of liposomal doxorubicin and number of cycles used was specified in the abstract. The doses of the other medications and schedule are provided based on the standard R-CHOP regimen, whose references can be found on this page.''
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Pegylated liposomal doxorubicin (Doxil)]] 30 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
'''21-day cycle for 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#Zaja F, Tomadini V, Zaccaria A, Lenoci M, Battista M, Molinari AL, Fabbri A, Battista R, Cabras MG, Gallamini A, Fanin R. CHOP-rituximab with pegylated liposomal doxorubicin for the treatment of elderly patients with diffuse large B-cell lymphoma. Leuk Lymphoma. 2006 Oct;47(10):2174-80. [https://doi.org/10.1080/10428190600799946 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17071492 PubMed]
 
−
#'''MDACC 2004-0305:''' Oki Y, Ewer MS, Lenihan DJ, Fisch MJ, Hagemeister FB, Fanale M, Romaguera J, Pro B, Fowler N, Younes A, Astrow AB, Huang X, Kwak LW, Samaniego F, McLaughlin P, Neelapu SS, Wang M, Fayad LE, Durand JB, Rodriguez MA. Pegylated liposomal doxorubicin replacing conventional doxorubicin in standard R-CHOP chemotherapy for elderly patients with diffuse large B-cell lymphoma: an open label, single arm, phase II trial. Clin Lymphoma Myeloma Leuk. 2015 Mar;15(3):152-8. Epub 2014 Sep 28. [http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(14)00411-X link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4344896/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25445468 PubMed] NCT00101010
 
−
==R-CEOP90 (Epirubicin, Prednisolone) {{#subobject:ebcd7e|Regimen=1}}==
 
−
R-CEOP90: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''pirubicin ('''<u>90</u>''' mg/m<sup>2</sup> dosing), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisolone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 4 cycles {{#subobject:d0b303|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.3109/10428194.2013.876632 Cai et al. 2014]
 
−
|NR in abstract
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Note: This regimen is intended to reduce cardiotoxicity and was not just for patients with contraindicated doxorubicin. Note that the cycle length is not explicitly defined in the paper but was reported as a median of 21 days (range 21 to 33 days).''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 2
 
−
*[[Epirubicin (Ellence)]] 90 mg/m<sup>2</sup> IV once on day 2
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 2
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisolone (Millipred)]] 100 mg/day PO on days 2 to 6
 
−
'''21-day cycle for 4 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients with stage IA or IIA disease with bulky disease and extranodal and residual masses: [[#Radiation_therapy|IFRT]], 30 to 45 Gy
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 6 cycles {{#subobject:d1cd34|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.3109/10428194.2013.876632 Cai et al. 2014]
 
−
|NR in abstract
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Note: This regimen is intended to reduce cardiotoxicity and was not just for patients with contraindicated doxorubicin. Note that the cycle length is not explicitly defined in the paper but was reported as a median of 21 days (range 21 to 33 days).''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 2
 
−
*[[Epirubicin (Ellence)]] 90 mg/m<sup>2</sup> IV once on day 2
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 2
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisolone (Millipred)]] 100 mg/day PO on days 2 to 6
 
−
'''21-day cycle for 6 cycles (see note)'''
 
−
</div></div>
 
−
===References===
 
−
#Cai QC, Gao Y, Wang XX, Cai QQ, Lin ZX, Bai B, Guo Y, Huang HQ. Long-term results of the R-CEOP90 in the treatment of young patients with chemotherapy-naïve diffuse large B cell lymphoma: a phase II study. Leuk Lymphoma. 2014 Oct;55(10):2387-8. [https://doi.org/10.3109/10428194.2013.876632 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24528221 PubMed]
 
−
==R-CEOP (Etoposide) {{#subobject:dfb13d|Regimen=1}}==
 
−
R-CEOP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>E</u>'''toposide, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:d69b11|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://abstracts.hematologylibrary.org/cgi/content/abstract/114/22/408 Moccia et al. 2009]
 
−
| style="background-color:#ffffbe" |Retrospective
 
−
|-
 
−
|}
 
−
''Note: This regimen is intended for patients with a contraindication to anthracyclines. Only the dose of etoposide and number of cycles used was specified in the abstract. The doses of the other medications and schedule are provided based on the standard R-CHOP regimen, whose references can be found on this page.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup> IV once on day 1, then 100 mg/m<sup>2</sup> PO once per day on days 2 & 3
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
**Alternate dosing used in the R-CHOP regimens described in Coiffier et al. 2002 & 2010; Feugier et al. 2005; Mounier et al. 2012 - LNH 98-5 is [[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
'''21-day cycle for 3 to 4 cycles +/- radiation therapy for patients with limited stage disease; 6 cycles for patients with advanced stage disease'''
 
−
</div></div>
 
−
===References===
 
−
#'''Retrospective:''' '''Abstract:''' Moccia, Alden A., Schaff, Kimberly, Hoskins, Paul, Klasa, Richard, Savage, Kerry J., Shenkier, Tamara, Gascoyne, Randy D., Connors, Joseph M., Sehn, Laurie H. R-CHOP with Etoposide Substituted for Doxorubicin (R-CEOP): Excellent Outcome in Diffuse Large B Cell Lymphoma for Patients with a Contraindication to Anthracyclines. ASH Annual Meeting Abstracts 2009 114: 408 [http://abstracts.hematologylibrary.org/cgi/content/abstract/114/22/408 link to abstract]
 
−
==R-GCVP {{#subobject:dff264|Regimen=1}}==
 
−
R-GCVP: '''<u>R</u>'''ituximab, '''<u>G</u>'''emcitabine, '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''incristine, '''<u>P</u>'''rednisolone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:dad22|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2013.49.7586 Fields et al. 2013 (UCL/05/154)]
 
−
|2008-2010
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Intended for use in patients unlikely to tolerate anthracyclines due to cardiac comorbidity.''
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Gemcitabine (Gemzar)]] as follows:
 
−
**Cycle 1: 750 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8
 
−
**Cycle 2: 875 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8
 
−
**Cycles 3 to 6: 1000 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisolone (Millipred)]] 100 mg PO once per day on days 1 to 5
 
−
====Supportive therapy====
 
−
*[[Acetaminophen (Tylenol)]] 1000 mg (route not specified) once on day 1, prior to [[Rituximab (Rituxan)]]
 
−
*[[Chlorpheniramine (Chlor-Trimeton)]] 10 mg IV once on day 1, prior to [[Rituximab (Rituxan)]]
 
−
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 9
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] 12.5 mg IT x 3 cycles (timing not specified) for patients at high risk of CNS relapse
 
−
'''21-day cycle for 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- Presented at the 53rd Annual Meeting of the American Society of Hematology, San Diego, CA, December 10-13, 2011. -->
 
−
#'''UCL/05/154:''' Fields PA, Townsend W, Webb A, Counsell N, Pocock C, Smith P, Jack A, El-Mehidi N, Johnson PW, Radford J, Linch DC, Cunningham D. De novo treatment of diffuse large B-cell lymphoma with rituximab, cyclophosphamide, vincristine, gemcitabine, and prednisolone in patients with cardiac comorbidity: a United kingdom national cancer research institute trial. J Clin Oncol. 2014 Feb 1;32(4):282-7. Epub 2013 Nov 12. [https://doi.org/10.1200/jco.2013.49.7586 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24220559 PubMed] NCT00971763
 
−
==R-MegaCHOP {{#subobject:4e9b3e|Regimen=1}}==
 
−
R-MegaCHOP: '''<u>R</u>'''ituximab, Mega, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''redniso(lo)ne
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:c3f62c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.13036 Pardal et al. 2014 (GELTAMO-2006)]
 
−
|2007-2009
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 1500 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 65 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
====Supportive therapy====
 
−
*[[Pegfilgrastim (Neulasta)]] given after each cycle
 
−
'''21-day cycle for 3 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Negative PET-CT after 3 cycles: [[#R-MegaCHOP|R-MegaCHOP]] x 3 for a total of 6 cycles
 
−
*Positive PET-CT after 3 cycles: [[#R-IFE_2|R-IFE]]
 
−
</div></div>
 
−
===References===
 
−
#'''GELTAMO-2006:''' Pardal E, Coronado M, Martín A, Grande C, Marín-Niebla A, Panizo C, Bello JL, Conde E, Hernández MT, Arranz R, Bargay J, González-Barca E, Pérez-Ceballos E, Montes-Moreno S, Caballero MD. Intensification treatment based on early FDG-PET in patients with high-risk diffuse large B-cell lymphoma: a phase II GELTAMO trial. Br J Haematol. 2014 Nov;167(3):327-36. Epub 2014 Jul 28. [https://doi.org/10.1111/bjh.13036 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25066542 PubMed] NCT013611091
 
−
==R-miniCHOP {{#subobject:17bb83|Regimen=1}}==
 
−
R-miniCHOP: '''<u>R</u>'''ituximab, reduced-dose ('''mini''') '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''redniso(lo)ne
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:9fd3ee|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(11)70069-9 Peyrade et al. 2011 (LNH03-7B)]
 
−
|2006-2009
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 400 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vincristine (Oncovin)]] 1 mg IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
−
====Supportive therapy====
 
−
*"Prevention of tumour lysis syndrome by alkalinisation or hypouricaemic drugs was done if necessary."
 
−
*[[:Category:Serotonin_5-HT3_antagonists | Serotonin (5-HT3) antagonist]] given every cycle.
 
−
*Prophylactic [[Filgrastim (Neupogen) | G-CSF]] or erythropoietin was left to treating physician's discretion.
 
−
**Patients with severe neutropenia or neutropenic fever received [[Filgrastim (Neupogen) | G-CSF]] (dose not specified) SC once per day on days 6 to 13 of the subsequent cycle until ANC is greater than or equal to 1000/uL.
 
−
'''21-day cycle for 6 cycles'''
 
−
====Dose modifications====
 
−
*No dose adjustments for hematologic toxicity. If needed, the subsequent R-miniCHOP cycle was postponed until ANC was greater than or equal to 1000/uL and platelet count was greater than or equal to 100 x 10<sup>9</sup>/L, with a maximum of 28 days between cycles. Treatment was stopped if patients' counts were not adequate within 28 days.
 
−
</div></div>
 
−
===References===
 
−
#'''LNH03-7B:''' Peyrade F, Jardin F, Thieblemont C, Thyss A, Emile JF, Castaigne S, Coiffier B, Haioun C, Bologna S, Fitoussi O, Lepeu G, Fruchart C, Bordessoule D, Blanc M, Delarue R, Janvier M, Salles B, André M, Fournier M, Gaulard P, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. Attenuated immunochemotherapy regimen (R-miniCHOP) in elderly patients older than 80 years with diffuse large B-cell lymphoma: a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2011 May;12(5):460-8. [https://doi.org/10.1016/S1470-2045(11)70069-9 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21482186 PubMed] NCT01087424
 
−
#'''SWOG S1918:''' NCT04799275
 
−
=Consolidation after upfront therapy=
 
−
==CBV, then auto HSCT {{#subobject:fccfc5|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:00b635|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985418/ Stiff et al. 2013 (SWOG S9704)]
 
−
|1999-2007
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#R-CHOP|R-CHOP]] x 8
 
−
| style="background-color:#1a9850" |Superior PFS<br>PFS24: 69% vs 55%<br>(HR 0.58, 95% CI 0.40-0.85)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#R-CHOP|R-CHOP]] x 6
 
−
{{#lst:Autologous HSCT conditioning regimens|6fc278}}
 
−
</div></div>
 
−
===References===
 
−
#'''SWOG S9704:''' Stiff PJ, Unger JM, Cook JR, Constine LS, Couban S, Stewart DA, Shea TC, Porcu P, Winter JN, Kahl BS, Miller TP, Tubbs RR, Marcellus D, Friedberg JW, Barton KP, Mills GM, LeBlanc M, Rimsza LM, Forman SJ, Fisher RI. Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma. N Engl J Med. 2013 Oct 31;369(18):1681-90. [https://doi.org/10.1056/NEJMoa1301077 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985418/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24171516 PubMed] NCT00004031
 
−
##'''Subgroup analysis:''' Puvvada SD, Stiff PJ, Leblanc M, Cook JR, Couban S, Leonard JP, Kahl B, Marcellus D, Shea TC, Winter JN, Li H, Rimsza LM, Friedberg JW, Smith SM. Outcomes of MYC-associated lymphomas after R-CHOP with and without consolidative autologous stem cell transplant: subset analysis of randomized trial intergroup SWOG S9704. Br J Haematol. 2016 Sep;174(5):686-91. Epub 2016 Apr 13. [https://doi.org/10.1111/bjh.14100 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125530/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27072903 PubMed]
 
−
==CBVM, then auto HSCT {{#subobject:59bb2c|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:bbedec|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdp237 Haioun et al. 2009 (LNH 98-3)]
 
−
|1999-2004
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Preceding treatment====
 
−
*[[Diffuse_large_B-cell_lymphoma_-_historical#ACE|ACE]] versus [[Diffuse_large_B-cell_lymphoma_-_historical#ACVBP|ACVBP]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Carmustine (BCNU)]]
 
−
*[[Etoposide (Vepesid)]]
 
−
*[[Cyclophosphamide (Cytoxan)]]
 
−
*[[Mitoxantrone (Novantrone)]]
 
−
'''Stem cells reinfused afterwards (unclear which day)'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[Diffuse_large_B-cell_lymphoma_-_null_regimens#Observation|Observation]] versus [[#Rituximab_monotherapy|rituximab]] maintenance
 
−
</div></div>
 
−
===References===
 
−
#'''LNH 98-3:''' Haioun C, Mounier N, Emile JF, Ranta D, Coiffier B, Tilly H, Récher C, Fermé C, Gabarre J, Herbrecht R, Morchhauser F, Gisselbrecht C. Rituximab versus observation after high-dose consolidative first-line chemotherapy with autologous stem-cell transplantation in patients with poor-risk diffuse large B-cell lymphoma. Ann Oncol. 2009 Dec;20(12):1985-92. Epub 2009 Jun 30. [https://doi.org/10.1093/annonc/mdp237 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19567453 PubMed]
 
−
==Cytarabine monotherapy {{#subobject:fa5ce3|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:4f9fa6|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(11)61040-4 Récher et al. 2011 (LNH03-2B)]
 
−
|2003-2008
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase III RCT
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mds600 Ketterer et al. 2013 (LNH03-1B)]
 
−
|2003-2008
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase III RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#R-IFE|REI]] consolidation x 4
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> SC once per day on days 1 to 4
 
−
'''14-day cycle for 2 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''LNH03-2B:''' Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O, Thiéblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquières H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais JP, Salles G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011 Nov 26;378(9806):1858-67. [https://doi.org/10.1016/S0140-6736(11)61040-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22118442 PubMed] NCT00140595
 
−
##'''Subgroup analysis:''' Molina TJ, Canioni D, Copie-Bergman C, Recher C, Brière J, Haioun C, Berger F, Fermé C, Copin MC, Casasnovas O, Thieblemont C, Petrella T, Leroy K, Salles G, Fabiani B, Morschauser F, Mounier N, Coiffier B, Jardin F, Gaulard P, Jais JP, Tilly H. Young patients with non-germinal center B-cell-like diffuse large B-cell lymphoma benefit from intensified chemotherapy with ACVBP plus rituximab compared with CHOP plus rituximab: analysis of data from the Groupe d'Etudes des Lymphomes de l'Adulte/lymphoma study association phase III trial LNH 03-2B. J Clin Oncol. 2014 Dec 10;32(35):3996-4003. Epub 2014 Nov 10. [https://doi.org/10.1200/JCO.2013.54.9493 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25385729 PubMed]
 
−
#'''LNH03-1B:''' Ketterer N, Coiffier B, Thieblemont C, Fermé C, Brière J, Casasnovas O, Bologna S, Christian B, Connerotte T, Récher C, Bordessoule D, Fruchart C, Delarue R, Bonnet C, Morschhauser F, Anglaret B, Soussain C, Fabiani B, Tilly H, Haioun C. Phase III study of ACVBP versus ACVBP plus rituximab for patients with localized low-risk diffuse large B-cell lymphoma (LNH03-1B). Ann Oncol. 2013 Apr;24(4):1032-7. Epub 2012 Dec 12. [https://doi.org/10.1093/annonc/mds600 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23235801 PubMed] NCT00140595
 
−
==Ibritumomab tiuxetan protocol {{#subobject:85625d|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, no cap {{#subobject:a989fb|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691189/ Witzig et al. 2015 (ECOG E3402)]
 
−
|2004-2008
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#R-CHOP|R-CHOP]] x 4 to 6
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 250 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
====Radioconjugate therapy====
 
−
*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin)]] 14.8 MBq/kg IV once on day 8
 
−
'''8-day course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients with CT or PET positive disease 12 weeks after radioimmunotherapy: [[#Radiation_therapy|30 Gy of IFRT]]
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, capped dose {{#subobject:dfc019|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287635/ Persky et al. 2014 (SWOG S0313)]
 
−
|2004-2008
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]] x 3, then [[#Radiation_therapy|IFRT]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 250 mg/m<sup>2</sup> IV once per day on days 1 & 8 +/- 1 day, '''given first on day 7, 8, or 9'''
 
−
====Radioconjugate therapy====
 
−
*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin)]] 0.4 mCi/kg (maximum dose of 32 mCi) IV once on day 8 +/- 1 day, '''given second, within 4 hours of rituximab'''
 
−
</div></div>
 
−
===References===
 
−
#'''SWOG S0313:''' Persky DO, Miller TP, Unger JM, Spier CM, Puvvada S, Stea BD, Press OW, Constine LS, Barton KP, Friedberg JW, LeBlanc M, Fisher RI. Ibritumomab consolidation after 3 cycles of CHOP plus radiotherapy in high-risk limited-stage aggressive B-cell lymphoma: SWOG S0313. Blood. 2015 Jan 8;125(2):236-41. Epub 2014 Nov 13. [http://www.bloodjournal.org/content/125/2/236.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287635/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25395425 PubMed] NCT00070018
 
−
#'''ECOG E3402:''' Witzig TE, Hong F, Micallef IN, Gascoyne RD, Dogan A, Wagner H Jr, Kahl BS, Advani RH, Horning SJ. A phase II trial of RCHOP followed by radioimmunotherapy for early stage (stages I/II) diffuse large B-cell non-Hodgkin lymphoma: ECOG3402. Br J Haematol. 2015 Sep;170(5):679-86. Epub 2015 May 14. [https://doi.org/10.1111/bjh.13493 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691189/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25974212 PubMed] NCT00088881
 
−
==Methotrexate monotherapy {{#subobject:d77e3a|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:b1d075|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(11)61040-4 Récher et al. 2011 (LNH03-2B)]
 
−
|2003-2008
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase III RCT
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mds600 Ketterer et al. 2013 (LNH03-1B)]
 
−
|2003-2008
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase III RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#R-ACVBP|R-ACVBP]] induction x 4
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV once on day 1
 
−
====Supportive therapy====
 
−
*[[Folinic acid (Leucovorin)|Calcium folinate - Folinic acid (Leucovorin)]] rescue
 
−
'''14-day cycle for 2 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#R-IFE|REI]] consolidation, in 2 weeks
 
−
</div></div>
 
−
===References===
 
−
#'''LNH03-2B:''' Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O, Thiéblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquières H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais JP, Salles G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011 Nov 26;378(9806):1858-67. [https://doi.org/10.1016/S0140-6736(11)61040-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22118442 PubMed] NCT00140595
 
−
##'''Subgroup analysis:''' Molina TJ, Canioni D, Copie-Bergman C, Recher C, Brière J, Haioun C, Berger F, Fermé C, Copin MC, Casasnovas O, Thieblemont C, Petrella T, Leroy K, Salles G, Fabiani B, Morschauser F, Mounier N, Coiffier B, Jardin F, Gaulard P, Jais JP, Tilly H. Young patients with non-germinal center B-cell-like diffuse large B-cell lymphoma benefit from intensified chemotherapy with ACVBP plus rituximab compared with CHOP plus rituximab: analysis of data from the Groupe d'Etudes des Lymphomes de l'Adulte/lymphoma study association phase III trial LNH 03-2B. J Clin Oncol. 2014 Dec 10;32(35):3996-4003. Epub 2014 Nov 10. [https://doi.org/10.1200/JCO.2013.54.9493 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25385729 PubMed]
 
−
#'''LNH03-1B:''' Ketterer N, Coiffier B, Thieblemont C, Fermé C, Brière J, Casasnovas O, Bologna S, Christian B, Connerotte T, Récher C, Bordessoule D, Fruchart C, Delarue R, Bonnet C, Morschhauser F, Anglaret B, Soussain C, Fabiani B, Tilly H, Haioun C. Phase III study of ACVBP versus ACVBP plus rituximab for patients with localized low-risk diffuse large B-cell lymphoma (LNH03-1B). Ann Oncol. 2013 Apr;24(4):1032-7. Epub 2012 Dec 12. [https://doi.org/10.1093/annonc/mds600 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23235801 PubMed] NCT00140595
 
−
==Radiation therapy {{#subobject:98e441|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, testicular irradiation {{#subobject:a72fd1|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2010.31.4187 Vitolo et al. 2011 (IELSG-10)]
 
−
|2001-2006
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#R-CHOP|R-CHOP]] x 6 to 8 cycles
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Radiotherapy====
 
−
*[[External beam radiotherapy]] 25 to 30 Gy to the contralateral testis. For patients with stage II disease, involved-field radiation therapy was added; see paper for details.
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, IFRT x 30 Gy {{#subobject:54f3d9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2004.06.088 Horning et al. 2004 (ECOG E1484)]
 
−
|1984-1992
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Diffuse_large_B-cell_lymphoma_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#91cf60" |Seems to have superior DFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*ECOG E1484: [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]] x 8, with CR
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Radiotherapy====
 
−
*[[External beam radiotherapy|IFRT]] 30 Gy
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 36 Gy {{#subobject:214e87|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/104/3/634.long Pfreundschuh et al. 2004 (NHL-B2)]
 
−
|1993-2000
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045%2808%2970002-0 Pfreundschuh et al. 2008 (RICOVER-60)]
 
−
|2000-2005
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase III RCT
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(12)70481-3 Schmitz et al. 2012 (DSHNHL 2002-1)]
 
−
|2003-2009
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase III RCT
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2013.54.6861 Pfreundschuh et al. 2014 (SMARTE-R-CHOP-14)]
 
−
|2007-2009
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*NHL-B2: [[Diffuse_large_B-cell_lymphoma_-_historical#CHOEP-14|CHOEP-14]] x 6 versus [[Diffuse_large_B-cell_lymphoma_-_historical#CHOEP-21|CHOEP-21]] x 6 versus [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP-14|CHOP-14]] x 6 versus [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP-21]] x 6
 
−
*RICOVER-60: [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP-14|CHOP-14]] x 6 versus [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP-14|CHOP-14]] x 8 versus [[#R-CHOP-14|R-CHOP-14]] x 6 versus [[#R-CHOP-14|R-CHOP-14]] x 8
 
−
*DSHNHL 2002-1: [[#R-CHOEP-14|R-CHOEP-14]] x 8 versus [[#R-MegaCHOEP_99|R-MegaCHOEP]]
 
−
*SMARTE-R-CHOP-14: [[#R-CHOP-14|R-CHOP-14]] x 6
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Radiotherapy====
 
−
*[[External beam radiotherapy]] 36 Gy in daily fractions
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #4, IFRT x 40 Gy {{#subobject:54f3d9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2004.06.088 Horning et al. 2004 (ECOG E1484)]
 
−
|1984-1992
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase III RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2006.07.0722 Bonnet et al. 2007]
 
−
|1993-2002
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Diffuse_large_B-cell_lymphoma_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287635/ Persky et al. 2014 (SWOG S0313)]
 
−
|2004-2008
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5757680/ Lamy et al. 2017 (LYSA/GOELAMS 02-03)]
 
−
|2005-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Diffuse_large_B-cell_lymphoma_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#eeee00" |Non-inferior EFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*ECOG E1484: [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]] x 8, with PR
 
−
*SWOG S0313: [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]] x 3, with CR
 
−
*Bonnet et al. 2007: [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]] x 4
 
−
*LYSA/GOELAMS 02-03: [[#R-CHOP-14|R-CHOP-14]] x 4 to 6
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Radiotherapy====
 
−
*[[External beam radiotherapy]] 40 Gy in daily fractions of 1.8 to 2 Gy
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*SWOG S0313: [[#Ibritumomab_tiuxetan_protocol|Ibritumomab tiuxetan]] consolidation
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #5, IFRT x 40 to 55 Gy {{#subobject:0cd919|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM199807023390104 Miller et al. 1998 (SWOG S8736)]
 
−
|1988-1995
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 
−
|[[Complex_multipart_regimens#SWOG_S8736|See link]]
 
−
|[[Complex_multipart_regimens#SWOG_S8736|See link]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2007.13.6929 Persky et al. 2008 (SWOG S0014)]
 
−
|2000-2002
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045%2806%2970664-7 Pfreundschuh et al. 2006 (NCIC-CTG LY.9)]
 
−
|2000-2003
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287635/ Persky et al. 2014 (SWOG S0313)]
 
−
|2004-2008
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|}
 
−
''Note: these studies did not specify an exact dose; see papers for details.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*SWOG S8736 and SWOG S0014: [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]] x 3
 
−
*NCIC-CTG LY.9: [[Regimen_classes#CHOP-like_therapy|CHOP-like therapy]] x 6 versus [[Regimen_classes#R-CHOP-like_therapy|R-CHOP-like therapy]] x 6
 
−
*SWOG S0313: [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]] x 3, with PR
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Radiotherapy====
 
−
*[[External beam radiotherapy]] 46 to 50 Gy in daily fractions of 1.8 to 2 Gy
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*SWOG S0313: [[#Ibritumomab_tiuxetan_protocol|Ibritumumoab tiuxetan]] consolidation
 
−
</div></div>
 
−
===References===
 
−
#'''SWOG S8736:''' Miller TP, Dahlberg S, Cassady JR, Adelstein DJ, Spier CM, Grogan TM, LeBlanc M, Carlin S, Chase E, Fisher RI. Chemotherapy alone compared with chemotherapy plus radiotherapy for localized intermediate- and high-grade non-Hodgkin's lymphoma. N Engl J Med. 1998 Jul 2;339(1):21-6. [https://doi.org/10.1056/NEJM199807023390104 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9647875 PubMed] NCT00005089
 
−
##'''Update:''' Stephens DM, Li H, LeBlanc ML, Puvvada SD, Persky D, Friedberg JW, Smith SM. Continued risk of relapse independent of treatment modality in limited-stage diffuse large B-cell lymphoma: Final and long-term analysis of Southwest Oncology Group study S8736. J Clin Oncol. 2016 Sep 1;34(25):2997-3004. Epub 2016 Jul 5. [https://doi.org/10.1200/jco.2015.65.4582 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5012710/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27382104 PubMed]
 
−
#'''NHL-B2:''' Pfreundschuh M, Trümper L, Kloess M, Schmits R, Feller AC, Rübe C, Rudolph C, Reiser M, Hossfeld DK, Eimermacher H, Hasenclever D, Schmitz N, Loeffler M; German High-Grade Non-Hodgkin's Lymphoma Study Group. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood. 2004 Aug 1;104(3):634-41. Epub 2004 Mar 11. [http://www.bloodjournal.org/content/104/3/634.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15016643 PubMed]
 
−
#'''ECOG E1484:''' Horning SJ, Weller E, Kim K, Earle JD, O'Connell MJ, Habermann TM, Glick JH. Chemotherapy with or without radiotherapy in limited-stage diffuse aggressive non-Hodgkin's lymphoma: Eastern Cooperative Oncology Group study 1484. J Clin Oncol. 2004 Aug 1;22(15):3032-8. Epub 2004 Jun 21. [https://doi.org/10.1200/jco.2004.06.088 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15210738 PubMed]
 
−
#'''LNH 93-01:''' Reyes F, Lepage E, Ganem G, Molina TJ, Brice P, Coiffier B, Morel P, Ferme C, Bosly A, Lederlin P, Laurent G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. ACVBP versus CHOP plus radiotherapy for localized aggressive lymphoma. N Engl J Med. 2005 Mar 24;352(12):1197-205. [https://doi.org/10.1056/NEJMoa042040 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15788496 PubMed]
 
−
#'''NCIC-CTG LY.9:''' Pfreundschuh M, Trümper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, López-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M; MabThera International Trial Group. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006 May;7(5):379-91. [https://doi.org/10.1016/S1470-2045%2806%2970664-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16648042 PubMed] NCT00064116
 
−
##'''Update:''' Pfreundschuh M, Kuhnt E, Trümper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, López-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N; MabThera International Trial (MInT) Group. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011 Oct;12(11):1013-22. [https://doi.org/10.1016/S1470-2045%2811%2970235-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21940214 PubMed]
 
−
#Bonnet C, Fillet G, Mounier N, Ganem G, Molina TJ, Thiéblemont C, Fermé C, Quesnel B, Martin C, Gisselbrecht C, Tilly H, Reyes F; Groupe d'Etude des Lymphomes de l'Adulte. CHOP alone compared with CHOP plus radiotherapy for localized aggressive lymphoma in elderly patients: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2007 Mar 1;25(7):787-92. Epub 2007 Jan 16. [https://doi.org/10.1200/JCO.2006.07.0722 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17228021 PubMed]
 
−
#'''RICOVER-60:''' Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, Reiser M, Nickenig C, Clemens M, Peter N, Bokemeyer C, Eimermacher H, Ho A, Hoffmann M, Mertelsmann R, Trümper L, Balleisen L, Liersch R, Metzner B, Hartmann F, Glass B, Poeschel V, Schmitz N, Ruebe C, Feller AC, Loeffler M; German High-Grade Non-Hodgkin Lymphoma Study Group. Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol. 2008 Feb;9(2):105-16. [https://doi.org/10.1016/S1470-2045%2808%2970002-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18226581 PubMed] NCT00052936
 
−
#'''SWOG S0014:''' Persky DO, Unger JM, Spier CM, Stea B, LeBlanc M, McCarty MJ, Rimsza LM, Fisher RI, Miller TP; [[Study_Groups#SWOG|SWOG]]. Phase II study of rituximab plus three cycles of CHOP and involved-field radiotherapy for patients with limited-stage aggressive B-cell lymphoma: Southwest Oncology Group study 0014. J Clin Oncol. 2008 May 10;26(14):2258-63. Epub 2008 Apr 14. [https://doi.org/10.1200/jco.2007.13.6929 link to original article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/18413640 PubMed]
 
−
#'''IELSG-10:''' Vitolo U, Chiappella A, Ferreri AJ, Martelli M, Baldi I, Balzarotti M, Bottelli C, Conconi A, Gomez H, Lopez-Guillermo A, Martinelli G, Merli F, Novero D, Orsucci L, Pavone V, Ricardi U, Storti S, Gospodarowicz MK, Cavalli F, Sarris AH, Zucca E. First-line treatment for primary testicular diffuse large B-cell lymphoma with rituximab-CHOP, CNS prophylaxis, and contralateral testis irradiation: final results of an international phase II trial. J Clin Oncol. 2011 Jul 10;29(20):2766-72. Epub 2011 Jun 6. [https://doi.org/10.1200/jco.2010.31.4187 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21646602 PubMed] NCT00210379
 
−
#'''DSHNHL 2002-1:''' Schmitz N, Nickelsen M, Ziepert M, Haenel M, Borchmann P, Schmidt C, Viardot A, Bentz M, Peter N, Ehninger G, Doelken G, Ruebe C, Truemper L, Rosenwald A, Pfreundschuh M, Loeffler M, Glass B; German High-Grade Lymphoma Study Group. Conventional chemotherapy (CHOEP-14) with rituximab or high-dose chemotherapy (MegaCHOEP) with rituximab for young, high-risk patients with aggressive B-cell lymphoma: an open-label, randomised, phase 3 trial (DSHNHL 2002-1). Lancet Oncol. 2012 Dec;13(12):1250-1259. Epub 2012 Nov 16. [https://doi.org/10.1016/S1470-2045(12)70481-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23168367 PubMed] NCT00129090
 
−
#'''SWOG S0313:''' Persky DO, Miller TP, Unger JM, Spier CM, Puvvada S, Stea BD, Press OW, Constine LS, Barton KP, Friedberg JW, LeBlanc M, Fisher RI. Ibritumomab consolidation after 3 cycles of CHOP plus radiotherapy in high-risk limited-stage aggressive B-cell lymphoma: SWOG S0313. Blood. 2015 Jan 8;125(2):236-41. Epub 2014 Nov 13. [http://www.bloodjournal.org/content/125/2/236.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287635/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25395425 PubMed] NCT00070018
 
−
#'''SMARTE-R-CHOP-14:''' Pfreundschuh M, Poeschel V, Zeynalova S, Hänel M, Held G, Schmitz N, Viardot A, Dreyling MH, Hallek M, Mueller C, Wiesen MH, Witzens-Harig M, Truemper L, Keller U, Rixecker T, Zwick C, Murawski N; German High-Grade Non-Hodgkin Lymphoma Study Group. Optimization of rituximab for the treatment of diffuse large B-cell lymphoma (II): extended rituximab exposure time in the SMARTE-R-CHOP-14 trial of the German High-Grade Non-Hodgkin Lymphoma Study Group. J Clin Oncol. 2014 Dec 20;32(36):4127-33. Epub 2014 Nov 17. Erratum in: J Clin Oncol. 2015 Jun 10;33(17):1991. [https://doi.org/10.1200/jco.2013.54.6861 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25403207 PubMed] NCT00052936
 
−
#'''LYSA/GOELAMS 02-03:''' Lamy T, Damaj G, Soubeyran P, Gyan E, Cartron G, Bouabdallah K, Gressin R, Cornillon J, Banos A, Le Du K, Benchalal M, Moles MP, Le Gouill S, Fleury J, Godmer P, Maisonneuve H, Deconinck E, Houot R, Laribi K, Marolleau JP, Tournilhac O, Branger B, Devillers A, Vuillez JP, Fest T, Colombat P, Costes V, Szablewski V, Béné MC, Delwail V; LYSA. R-CHOP 14 with or without radiotherapy in nonbulky limited-stage diffuse large B-cell lymphoma. Blood. 2018 Jan 11;131(2):174-181. Epub 2017 Oct 23. [http://www.bloodjournal.org/content/131/2/174.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5757680/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29061568 PubMed] NCT00841945
 
−
==R-IFE {{#subobject:62de3a|Regimen=1}}==
 
−
R-IFE: '''<u>R</u>'''ituximab, '''<u>IF</u>'''osfamide, '''<u>E</u>'''toposide
 
−
<br>REI: '''<u>R</u>'''ituximab, '''<u>E</u>'''toposide, '''<u>I</u>'''fosfamide
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:6de486|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(11)61040-4 Récher et al. 2011 (LNH03-2B)]
 
−
|2003-2008
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase III RCT
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mds600 Ketterer et al. 2013 (LNH03-1B)]
 
−
|2003-2008
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase III RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Methotrexate_monotherapy|Methotrexate]] consolidation x 2
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Etoposide (Vepesid)]] 300 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV once on day 1
 
−
'''14-day cycle for 4 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#Cytarabine_monotherapy|Cytarabine]] consolidation, in 2 weeks
 
−
</div></div>
 
−
===References===
 
−
#'''LNH03-2B:''' Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O, Thiéblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquières H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais JP, Salles G, Tilly H; Groupe d'Etude des Lymphomes de l'Adulte. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011 Nov 26;378(9806):1858-67. [https://doi.org/10.1016/S0140-6736(11)61040-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22118442 PubMed] NCT00140595
 
−
##'''Subgroup analysis:''' Molina TJ, Canioni D, Copie-Bergman C, Recher C, Brière J, Haioun C, Berger F, Fermé C, Copin MC, Casasnovas O, Thieblemont C, Petrella T, Leroy K, Salles G, Fabiani B, Morschauser F, Mounier N, Coiffier B, Jardin F, Gaulard P, Jais JP, Tilly H. Young patients with non-germinal center B-cell-like diffuse large B-cell lymphoma benefit from intensified chemotherapy with ACVBP plus rituximab compared with CHOP plus rituximab: analysis of data from the Groupe d'Etudes des Lymphomes de l'Adulte/lymphoma study association phase III trial LNH 03-2B. J Clin Oncol. 2014 Dec 10;32(35):3996-4003. Epub 2014 Nov 10. [https://doi.org/10.1200/JCO.2013.54.9493 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25385729 PubMed]
 
−
#'''LNH03-1B:''' Ketterer N, Coiffier B, Thieblemont C, Fermé C, Brière J, Casasnovas O, Bologna S, Christian B, Connerotte T, Récher C, Bordessoule D, Fruchart C, Delarue R, Bonnet C, Morschhauser F, Anglaret B, Soussain C, Fabiani B, Tilly H, Haioun C. Phase III study of ACVBP versus ACVBP plus rituximab for patients with localized low-risk diffuse large B-cell lymphoma (LNH03-1B). Ann Oncol. 2013 Apr;24(4):1032-7. Epub 2012 Dec 12. [https://doi.org/10.1093/annonc/mds600 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23235801 PubMed] NCT00140595
 
−
==TBI, then auto HSCT {{#subobject:37bf17|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:619e49|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985418/ Stiff et al. 2013 (SWOG S9704)]
 
−
|1999-2007
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#R-CHOP|R-CHOP]] x 8
 
−
| style="background-color:#1a9850" |Superior PFS<br>PFS24: 69% vs 55%<br>(HR 0.58, 95% CI 0.40-0.85)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#R-CHOP|R-CHOP]] x 6
 
−
{{#lst:Autologous HSCT conditioning regimens|635694}}
 
−
'''Stem cells reinfused on day 0'''
 
−
</div></div>
 
−
===References===
 
−
#'''SWOG S9704:''' Stiff PJ, Unger JM, Cook JR, Constine LS, Couban S, Stewart DA, Shea TC, Porcu P, Winter JN, Kahl BS, Miller TP, Tubbs RR, Marcellus D, Friedberg JW, Barton KP, Mills GM, LeBlanc M, Rimsza LM, Forman SJ, Fisher RI. Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma. N Engl J Med. 2013 Oct 31;369(18):1681-90. [https://doi.org/10.1056/NEJMoa1301077 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985418/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24171516 PubMed] NCT00004031
 
−
##'''Subgroup analysis:''' Puvvada SD, Stiff PJ, Leblanc M, Cook JR, Couban S, Leonard JP, Kahl B, Marcellus D, Shea TC, Winter JN, Li H, Rimsza LM, Friedberg JW, Smith SM. Outcomes of MYC-associated lymphomas after R-CHOP with and without consolidative autologous stem cell transplant: subset analysis of randomized trial intergroup SWOG S9704. Br J Haematol. 2016 Sep;174(5):686-91. Epub 2016 Apr 13. [https://doi.org/10.1111/bjh.14100 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125530/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27072903 PubMed]
 
−
==Z-BEAM, then auto HSCT {{#subobject:19f0d0|Regimen=1}}==
 
−
Z-BEAM: '''<u>Z</u>'''evalin (Ibritumomab tiuxetan), '''<u>B</u>'''iCNU (Carmustine), '''<u>E</u>'''toposide, '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''elphalan
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1 {{#subobject:9aeafe|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1002/cncr.27418 Shimoni et al. 2012 (SHEBA-07-4466-AN-CTIL)]
 
−
|NR
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 
−
|[[#BEAM|BEAM]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943314/ Briones et al. 2013 (GELTAMO Z-BEAM LDCGB)]
 
−
|2008-2010
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|}
 
−
{{#lst:Autologous HSCT|9aeafe}}
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2 {{#subobject:e7f161|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bbmt.org/article/S1083-8791(14)00473-X Fruchart et al. 2014 (ZBEAM2)]
 
−
|2007-2008
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Preceding treatment====
 
−
*[[#R-ACVBP|R-ACVBP]] or [[#R-CHOP|R-CHOP]]
 
−
{{#lst:Autologous HSCT|e7f161}}
 
−
</div></div>
 
−
===References===
 
−
#Shimoni A, Zwas ST, Oksman Y, Hardan I, Shem-Tov N, Yerushalmi R, Avigdor A, Ben-Bassat I, Nagler A. Yttrium-90-ibritumomab tiuxetan (Zevalin) combined with high-dose BEAM chemotherapy and autologous stem cell transplantation for chemo-refractory aggressive non-Hodgkin's lymphoma. Exp Hematol. 2007 Apr;35(4):534-40. [http://www.exphem.org/article/S0301-472X(07)00050-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17379063 PubMed]
 
−
#'''SHEBA-07-4466-AN-CTIL:''' Shimoni A, Avivi I, Rowe JM, Yeshurun M, Levi I, Or R, Patachenko P, Avigdor A, Zwas T, Nagler A. A randomized study comparing yttrium-90 ibritumomab tiuxetan (Zevalin) and high-dose BEAM chemotherapy versus BEAM alone as the conditioning regimen before autologous stem cell transplantation in patients with aggressive lymphoma. Cancer. 2012 Oct 1;118(19):4706-14. Epub 2012 Jan 17. [https://doi.org/10.1002/cncr.27418 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22252613 PubMed] NCT00491491
 
−
#'''GELTAMO Z-BEAM LDCGB:''' Briones J, Novelli S, García-Marco JA, Tomás JF, Bernal T, Grande C, Canales MA, Torres A, Moraleda JM, Panizo C, Jarque I, Palmero F, Hernández M, González-Barca E, López D, Caballero D. Autologous stem cell transplantation after conditioning with Yttrium-90 ibritumomab tiuxetan plus beam in refractory non-Hodgkin diffuse large B-cell lymphoma: results of a prospective, multicenter, phase II clinical trial. Haematologica. 2014 Mar;99(3):505-10. Epub 2013 Oct 25. [http://www.haematologica.org/content/99/3/505.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943314/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24162789 PubMed] EudraCT 2007-003198-22
 
−
#'''ZBEAM2:''' Fruchart C, Tilly H, Morschhauser F, Ghesquières H, Bouteloup M, Fermé C, Van Den Neste E, Bordessoule D, Bouabdallah R, Delmer A, Casasnovas RO, Ysebaert L, Ciappuccini R, Briere J, Gisselbrecht C. Upfront consolidation combining yttrium-90 ibritumomab tiuxetan and high-dose therapy with stem cell transplantation in poor-risk patients with diffuse large B cell lymphoma. Biol Blood Marrow Transplant. 2014 Dec;20(12):1905-11. Epub 2014 Jul 26. [http://www.bbmt.org/article/S1083-8791(14)00473-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25072780 PubMed] NCT00689169
 
−
=Maintenance after upfront therapy=
 
−
==Lenalidomide monotherapy {{#subobject:45aeb1|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 1 year {{#subobject:085502|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5214342/ Reddy et al. 2016 (VICC HEM 0835)]
 
−
|2008-2013
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-de-esc)
 
−
|[[#Lenalidomide_.26_Rituximab_88|Lenalidomide & Rituximab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of RFS12
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Preceding treatment====
 
−
*[[#R-CHOP|R-CHOP]] with or without radiation
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
 
−
'''28-day cycle for 12 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 2 years {{#subobject:9e4448|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2017.72.6984 Thieblemont et al. 2017 (REMARC)]
 
−
|2009-2014
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Diffuse_large_B-cell_lymphoma_-_null_regimens#Placebo|Placebo]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: NYR vs 58.9 mo<br>(HR 0.71, 95% CI 0.54-0.93)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#R-CHOP|R-CHOP-21]] or [[#R-CHOP-14|R-CHOP14]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
 
−
'''28-day cycle for up to 26 cycles (2 years)'''
 
−
</div></div>
 
−
===References===
 
−
#'''VICC HEM 0835:''' Reddy NM, Greer JP, Morgan DS, Chen H, Park SI, Richards KL. A phase II randomized study of lenalidomide or lenalidomide and rituximab as maintenance therapy following standard chemotherapy for patients with high/high-intermediate risk diffuse large B-cell lymphoma. Leukemia. 2017 Jan;31(1):241-244. Epub 2016 Sep 22. [https://doi.org/10.1038/leu.2016.255 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5214342/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27654851 PubMed] NCT00765245
 
−
<!-- # '''Abstract:''' Catherine Thieblemont, Hervé Tilly, Maria Gomez da Silva, Rene-Olivier Casasnovas, Christophe Fruchart, Franck Morschhauser, Corinne Haioun, Julien Lazarovici, Sebastian Grosicki, Aurore Perrot, Judith Trotman, Catherine Sebban, Dolores Caballero, Richard Greil, Koen Van Eygen, Josette Briere, Jose Cabecadas, Gilles Andre Salles, Philippe Gaulard, Andre Bosly and Bertrand Coiffier. First Analysis of an International Double-Blind Randomized Phase III Study of Lenalidomide Maintenance in Elderly Patients with DLBCL Treated with R-CHOP in First Line, the Remarc Study from Lysa. Blood 2016 128:471 [http://www.bloodjournal.org/content/128/22/471 link to abstract] -->
 
−
#'''REMARC:''' Thieblemont C, Tilly H, Gomes da Silva M, Casasnovas RO, Fruchart C, Morschhauser F, Haioun C, Lazarovici J, Grosicka A, Perrot A, Trotman J, Sebban C, Caballero D, Greil R, van Eygen K, Cohen AM, Gonzalez H, Bouabdallah R, Oberic L, Corront B, Choufi B, Lopez-Guillermo A, Catalano J, Van Hoof A, Briere J, Cabeçadas J, Salles G, Gaulard P, Bosly A, Coiffier B. Lenalidomide maintenance compared with placebo in responding elderly patients with diffuse large B-cell lymphoma treated with first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol. 2017 Aug 1;35(22):2473-2481. Epub 2017 Apr 20. [https://doi.org/10.1200/JCO.2017.72.6984 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28426350 PubMed] NCT01122472
 
−
==Rituximab monotherapy {{#subobject:c28fe4|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1 {{#subobject:da32ff|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4486230/ Jaeger et al. 2015 (NHL13)]
 
−
|2004-2010
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Diffuse_large_B-cell_lymphoma_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 
−
|-
 
−
|}
 
−
''Patients required to be in CR or CRu prior to enrollment. The protocol was amended after the first 69 patients enrolled to increase length of treatment from 1 to 2 years.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Regimen_classes#R-CHOP-like_therapy|R-CHOP-like chemotherapy]] x 4 to 8 (8 doses of rituximab)
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
'''2-month cycle for 6 to 12 cycles (1 to 2 years)'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2 {{#subobject:6c6458|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.13652 Witzens-Harig et al. 2015 (HD2002)]
 
−
|2002-2011
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Diffuse_large_B-cell_lymphoma_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#1a9850" |Superior OS in males
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*"Standard treatment" which was not further described in the paper, beyond that a majority of patient received [[#R-CHOP|R-CHOP]] (see Tables)
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
'''3-month cycle for 8 cycles (2 years)'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3 {{#subobject:7c3ba2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdp237 Haioun et al. 2009 (LNH 98-3)]
 
−
|1999-2004
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Diffuse_large_B-cell_lymphoma_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#d9ef8b" |Might have superior EFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#CBVM.2C_then_auto_HSCT|CBVM, then auto HSCT]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
'''4-week course'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #4 {{#subobject:8afe47|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.05.1003 Habermann et al. 2006 (ECOG E4494)]
 
−
|1998-2001
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Diffuse_large_B-cell_lymphoma_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of FFS
 
−
|-
 
−
|}
 
−
''Note: in ECOG E4494, rituximab maintenance had superior FFS in the group receiving [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]] upfront, which is no longer standard of care.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#R-CHOP|R-CHOP]] versus [[Diffuse_large_B-cell_lymphoma_-_historical#CHOP|CHOP]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
'''6-month cycle for 4 cycles (2 years)'''
 
−
</div></div>
 
−
===References===
 
−
#'''ECOG E4494:''' Habermann TM, Weller EA, Morrison VA, Gascoyne RD, Cassileth PA, Cohn JB, Dakhil SR, Woda B, Fisher RI, Peterson BA, Horning SJ. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006 Jul 1;24(19):3121-7. Epub 2006 Jun 5. [https://doi.org/10.1200/jco.2005.05.1003 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16754935 PubMed] NCT00003150
 
−
#'''LNH 98-3:''' Haioun C, Mounier N, Emile JF, Ranta D, Coiffier B, Tilly H, Récher C, Fermé C, Gabarre J, Herbrecht R, Morchhauser F, Gisselbrecht C. Rituximab versus observation after high-dose consolidative first-line chemotherapy with autologous stem-cell transplantation in patients with poor-risk diffuse large B-cell lymphoma. Ann Oncol. 2009 Dec;20(12):1985-92. Epub 2009 Jun 30. [https://doi.org/10.1093/annonc/mdp237 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19567453 PubMed]
 
−
<!-- These data have been presented in part at the 55th Annual Meeting of the American Society of Hematology, New Orleans 2013, the 12th International Conference on Malignant Lymphoma 2013, Lugano, and the 18th Congress of the European Hematology Association, Stockholm 2013. -->
 
−
#'''NHL13:''' Jaeger U, Trneny M, Melzer H, Praxmarer M, Nawarawong W, Ben Yehuda D, Goldstein D, Mihaljevic B, Ilhan O, Ballova V, Hedenus M, Hsiao LT, Au WY, Burgstaller S, Weidinger G, Keil F, Dittrich C, Skrabs C, Klingler A, Chott A, Fridrik MA, Greil R. Rituximab maintenance for patients with aggressive B-cell lymphoma in first remission: results of the randomized NHL13 trial. Haematologica. 2015 Jul;100(7):955-63. Epub 2015 Apr 24. [http://www.haematologica.org/content/100/7/955 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4486230/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25911553 PubMed] NCT00400478
 
−
#'''HD2002:''' Witzens-Harig M, Benner A, McClanahan F, Klemmer J, Brandt J, Brants E, Rieger M, Meissner J, Hensel M, Neben K, Dreger P, Lengfelder E, Schmidt-Wolf I, Krämer A, Ho AD. Rituximab maintenance improves survival in male patients with diffuse large B-cell lymphoma: results of the HD2002 prospective multicentre randomized phase III trial. Br J Haematol. 2015 Dec;171(5):710-9. Epub 2015 Oct 9. [https://doi.org/10.1111/bjh.13652 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26449739 PubMed] NCT01933711
 
−
=Relapsed or refractory, salvage therapy=
 
−
==Axicabtagene ciloleucel monotherapy {{#subobject:ug71xd|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:xb0jt6|Variant=1}}===
 
−
{| class="wikitable" style="color:white; background-color:#404040"
 
−
|<small>'''FDA-recommended dose'''</small>
 
−
|-
 
−
|}
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa2116133 Locke et al. 2021 (ZUMA-7)]
 
−
|2018-2019
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc)
 
−
|1. [[#R-ICE|R-ICE]]<br>2. [[#R-ESHAP|R-ESHAP]]<br>3. [[#R-DHAP|R-DHAP]]<br>4. [[#R-GDP|R-GDP]]
 
−
| style="background-color:#1a9850" |Superior EFS<br>Median EFS: 8.3 vs 2 mo<br>(HR 0.40, 95% CI 0.31-0.51)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*Failure of first-line chemoimmunotherapy including an [[Regimen_classes#Anti-CD20-based_regimen|anti-CD20 monoclonal antibody]] and an [[Regimen_classes#Anthracycline-based_regimen|anthracycline-containing regimen]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy, lymphodepletion====
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once per day on days -5 to -3 prior to [[Axicabtagene ciloleucel (Yescarta)|Axicabtagene ciloleucel]] infusion
 
−
*[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days -5 to -3 prior to [[Axicabtagene ciloleucel (Yescarta)|Axicabtagene ciloleucel]] infusion
 
−
====Immunotherapy====
 
−
*[[Axicabtagene ciloleucel (Yescarta)]] target dose of 2 × 10<sup>6</sup> CAR T cells/kg IV once on day 0
 
−
'''One course'''
 
−
</div></div>
 
−
===References===
 
−
#'''ZUMA-7:''' Locke FL, Miklos DB, Jacobson CA, Perales MA, Kersten MJ, Oluwole OO, Ghobadi A, Rapoport AP, McGuirk J, Pagel JM, Muñoz J, Farooq U, van Meerten T, Reagan PM, Sureda A, Flinn IW, Vandenberghe P, Song KW, Dickinson M, Minnema MC, Riedell PA, Leslie LA, Chaganti S, Yang Y, Filosto S, Shah J, Schupp M, To C, Cheng P, Gordon LI, Westin JR; All ZUMA-7 Investigators and Contributing Kite Members. Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma. N Engl J Med. 2022 Feb 17;386(7):640-654. Epub 2021 Dec 11. [https://doi.org/10.1056/nejmoa2116133 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34891224/ PubMed] NCT03391466
 
−
==Lisocabtagene maraleucel monotherapy {{#subobject:8u3u14|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:6nhr26|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/s0140-6736(22)00662-6 Kamdar et al. 2022 (TRANSFORM)]
 
−
|2018-2020
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc)
 
−
|1. [[#R-ICE|R-ICE]]<br>2. [[#R-DHAP|R-DHAP]]<br>3. [[#R-GDP|R-GDP]]
 
−
| style="background-color:#1a9850" |Superior EFS<br>Median EFS: 10.1 vs 2.3 mo<br>(HR 0.35, 95% CI 0.23-0.53)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Lisocabtagene maraleucel (Breyanzi)]]
 
−
</div></div>
 
−
===References===
 
−
#'''TRANSFORM:''' Kamdar M, Solomon SR, Arnason J, Johnston PB, Glass B, Bachanova V, Ibrahimi S, Mielke S, Mutsaers P, Hernandez-Ilizaliturri F, Izutsu K, Morschhauser F, Lunning M, Maloney DG, Crotta A, Montheard S, Previtali A, Stepan L, Ogasawara K, Mack T, Abramson JS; TRANSFORM Investigators. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022 Jun 18;399(10343):2294-2308. [https://doi.org/10.1016/s0140-6736(22)00662-6 link to original article]  [https://pubmed.ncbi.nlm.nih.gov/35717989/ PubMed] NCT03575351
 
−
==O-DHAP {{#subobject:49372b|Regimen=1}}==
 
−
O-DHAP: '''<u>O</u>'''fatumumab, '''<u>D</u>'''examethasone, '''<u>H</u>'''igh-dose '''<u>A</u>'''ra-C (Cytarabine), '''<u>P</u>'''latinol (Cisplatin)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:294f6d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3724189/ Matasar et al. 2013 (GSK 110927)]
 
−
|2009-2011
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2016.69.0198 van Imhoff et al. 2016 (ORCHARRD)]
 
−
|2010-2013
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#R-DHAP|R-DHAP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Ofatumumab (Arzerra)]] as follows:
 
−
**Cycle 1: 1000 mg IV once per day on days 1 & 8
 
−
**Cycles 2 & 3: 1000 mg IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg IV or PO once per day on days 1 to 4
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV every 12 hours on day 2 (total dose per cycle: 4000 mg/m<sup>2</sup>)
 
−
*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
 
−
====Supportive therapy====
 
−
*GSK 110927 recommended: [[Filgrastim (Neupogen)]] or [[Pegfilgrastim (Neulasta)]]
 
−
'''21-day cycle for 3 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*GSK 110927, responders: Stem-cell mobilization and [[Regimen_classes#High-dose_chemotherapy_with_auto_HSCT|autologous hematopoietic stem cell transplant (regimen not specified)]]
 
−
*ORCHARRD, responders: [[#BEAM.2C_then_auto_HSCT|BEAM with autologous hematopoietic stem cell transplant]] except those in Japan who received [[#LEED.2C_then_auto_HSCT|LEED with autologous hematopoietic stem cell transplant]]
 
−
</div></div>
 
−
===References===
 
−
<!-- Presented at the 2011 American Society of Hematology Annual Meeting, San Diego, CA, December 10-13, 2011. -->
 
−
#'''GSK 110927:''' Matasar MJ, Czuczman MS, Rodriguez MA, Fennessy M, Shea TC, Spitzer G, Lossos IS, Kharfan-Dabaja MA, Joyce R, Fayad L, Henkel K, Liao Q, Edvardsen K, Jewell RC, Fecteau D, Singh RP, Lisby S, Moskowitz CH. Ofatumumab in combination with ICE or DHAP chemotherapy in relapsed or refractory intermediate grade B-cell lymphoma. Blood. 2013 Jul 25;122(4):499-506. Epub 2013 May 21. [http://www.bloodjournal.org/content/122/4/499.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3724189/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23692856 PubMed] NCT00823719
 
−
#'''ORCHARRD:''' van Imhoff GW, McMillan A, Matasar MJ, Radford J, Ardeshna KM, Kuliczkowski K, Kim W, Hong X, Goerloev JS, Davies A, Barrigón MD, Ogura M, Leppä S, Fennessy M, Liao Q, van der Holt B, Lisby S, Hagenbeek A. Ofatumumab versus rituximab salvage chemoimmunotherapy in relapsed or refractory diffuse large B-cell lymphoma: The ORCHARRD study. J Clin Oncol. 2017 Feb 10;35(5):544-51. Epub 2016 Dec 28. [https://doi.org/10.1200/JCO.2016.69.0198 link to original article] [https://ascopubs.org/doi/suppl/10.1200/JCO.2016.69.0198/suppl_file/ds_2016.690198.pdf link to data supplement] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28029326 PubMed] NCT01014208
 
−
==O-ICE {{#subobject:f3f288|Regimen=1}}==
 
−
O-ICE: '''<u>O</u>'''fatumumab, '''<u>I</u>'''fosfamide, '''<u>C</u>'''arboplatin, '''<u>E</u>'''toposide
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:abb23b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3724189/ Matasar et al. 2013 (GSK 110927)]
 
−
|2009-2011
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Note: Subsequent consolidation therapy was not specified.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Ofatumumab (Arzerra)]] as follows:
 
−
**Cycle 1: 1000 mg IV once per day on days 1 & 8
 
−
**Cycles 2 & 3: 1000 mg IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Ifosfamide (Ifex)]] 5000 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 2, '''mixed with mesna'''
 
−
*[[Carboplatin (Paraplatin)]] AUC 5 (maximum dose of 800 mg) IV once on either day 1 or 2
 
−
**Carboplatin AUC calculated based on a 12-hour creatinine clearance
 
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
====Supportive therapy====
 
−
*[[Mesna (Mesnex)]] 5000 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 2, '''mixed with [[Ifosfamide (Ifex)]]'''
 
−
*Recommended: [[Filgrastim (Neupogen)]] or [[Pegfilgrastim (Neulasta)]]
 
−
'''21-day cycle for 3 cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- Presented at the 2011 American Society of Hematology Annual Meeting, San Diego, CA, December 10-13, 2011. -->
 
−
#'''GSK 110927:''' Matasar MJ, Czuczman MS, Rodriguez MA, Fennessy M, Shea TC, Spitzer G, Lossos IS, Kharfan-Dabaja MA, Joyce R, Fayad L, Henkel K, Liao Q, Edvardsen K, Jewell RC, Fecteau D, Singh RP, Lisby S, Moskowitz CH. Ofatumumab in combination with ICE or DHAP chemotherapy in relapsed or refractory intermediate grade B-cell lymphoma. Blood. 2013 Jul 25;122(4):499-506. Epub 2013 May 21. [http://www.bloodjournal.org/content/122/4/499.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3724189/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23692856 PubMed] NCT00823719
 
−
==R-DexaBEAM {{#subobject:81a0a4|Regimen=1}}==
 
−
R-DexaBEAM: '''<u>R</u>'''ituximab, '''<u>Dexa</u>'''methasone, '''<u>B</u>'''iCNU (Carmustine), '''<u>E</u>'''toposide, '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''elphalan
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:801417|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.13234 Kirschey et al. 2014 (Mz-135)]
 
−
|2002-2006
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Note: the dosing in the manuscript is different than below. The below are the correct doses as verified by the authors.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 8 mg PO three times per day on days 1 to 10
 
−
====Chemotherapy====
 
−
*[[Carmustine (BCNU)]] 60 mg/m<sup>2</sup> IV once on day 3
 
−
*[[Etoposide (Vepesid)]] 75 mg/m<sup>2</sup> IV once per day on days 4 to 7
 
−
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup> IV twice per day on days 4 to 7
 
−
*[[Melphalan (Alkeran)]] 20 mg/m<sup>2</sup> IV once on day 2
 
−
'''3- to 4-week cycle for 2 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#R-BEAM.2C_then_auto_HSCT|R-BEAM with autologous hematopoietic stem cell transplant]] or [[#R-TBI.2FCy.2C_then_auto_HSCT|R-TBI/Cy with autologous hematopoietic stem cell transplant]]
 
−
</div></div>
 
−
===References===
 
−
#'''Mz-135:''' Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. [https://doi.org/10.1111/bjh.13234 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25546611 PubMed] NCT02099292
 
−
==R-DHAOx {{#subobject:0d0c67|Regimen=1}}==
 
−
R-DHAOx: '''<u>R</u>'''ituximab, '''<u>D</u>'''examethasone, '''<u>H</u>'''igh-dose '''<u>A</u>'''ra-C (Cytarabine), '''<u>O</u>'''xaliplatin
 
−
<br>ROAD: '''<u>R</u>'''ituximab, '''<u>O</u>'''xaliplatin, '''<u>A</u>'''ra-C (Cytarabine), '''<u>D</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:962cf0|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1002/ajh.24824 Witzig et al. 2017 (MCCRC MC0485)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|2006-2008
 
−
| style="background-color:#bfd3e6" |ORR: 71% (95% CI, 56–84)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg IV or PO once per day on days 2 to 5
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 3 hours once per day on days 2 & 3, second dose to be given no sooner than 12 hours and no later than 24 hours after '''end''' of first dose
 
−
*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV over 2 hours once on day 2
 
−
====Supportive therapy====
 
−
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 4
 
−
'''21-day cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Most responders proceeded to high-dose chemotherapy with autologous hematopoietic stem cell transplant after 2 cycles, although this was not mandated in the protocol
 
−
</div></div>
 
−
===References===
 
−
#'''MCCRC MC0485:''' Witzig TE, Johnston PB, LaPlant BR, Kurtin PJ, Pederson LD, Moore DF Jr, Nabbout NH, Nikcevich DA, Rowland KM, Grothey A. Long-term follow-up of chemoimmunotherapy with rituximab, oxaliplatin, cytosine arabinoside, dexamethasone (ROAD) in patients with relapsed CD20+ B-cell non-Hodgkin lymphoma: Results of a study of the Mayo Clinic Cancer Center Research Consortium (MCCRC) MC0485 now known as academic and community cancer research united (ACCRU). Am J Hematol. 2017 Oct;92(10):1004-1010. Epub 2017 Aug 17. [https://doi.org/10.1002/ajh.24824 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28614905 PubMed] NCT00166439
 
−
==R-DHAP {{#subobject:18c266|Regimen=1}}==
 
−
R-DHAP: '''<u>R</u>'''ituximab, '''<u>D</u>'''examethasone, '''<u>H</u>'''igh-dose '''<u>A</u>'''ra-C (Cytarabine), '''<u>P</u>'''latinol (Cisplatin)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1 {{#subobject:af0858|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664033/ Gisselbrecht et al. 2010 (CORAL)]
 
−
|2003-2007
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#R-ICE|R-ICE]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of mobilization-adjusted response rate after 3 cycles
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2016.69.0198 van Imhoff et al. 2016 (ORCHARRD)]
 
−
|2010-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#O-DHAP|O-DHAP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|}
 
−
''Note: CORAL makes reference to Velasquez et al. 1988 to describe this regimen, although this reference is for DHAP, not R-DHAP. The paper also contains the following regimen information:''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] as follows, '''given first''':
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days -1 & 1 ('''CORAL''') or days 1 & 8 ('''ORCHARRD''')
 
−
**Cycle 2: 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on day 2 (total dose per cycle: 4000 mg/m<sup>2</sup>)
 
−
*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
 
−
====Supportive therapy====
 
−
*'''CORAL''': [[Filgrastim (Neupogen) | G-CSF]] "depending on site policy, with R-DHAP, but always after the third cycle until the end of leukaphereses"
 
−
'''21-day cycle for 3 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*CORAL, responders: [[#BEAM.2C_then_auto_HSCT|BEAM with autologous hematopoietic stem cell transplant]]
 
−
*ORCHARRD, responders: [[#BEAM.2C_then_auto_HSCT|BEAM with autologous hematopoietic stem cell transplant]] except those in Japan who received [[#LEED.2C_then_auto_HSCT|LEED with autologous hematopoietic stem cell transplant]]
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2 {{#subobject:ac829f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2013.53.9593 Crump et al. 2014 (NCIC-CTG LY.12)]
 
−
|2003-2011
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#R-GDP|R-GDP]]
 
−
| style="background-color:#eeee01" |Non-inferior RR after 2 cycles
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa2116133 Locke et al. 2021 (ZUMA-7)]
 
−
|2018-2019
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Axicabtagene_ciloleucel_monotherapy|Axicabtagene ciloleucel]]
 
−
| style="background-color:#d73027" |Inferior EFS
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa2116596 Bishop et al. 2021 (BELINDA)]
 
−
|2019-2021
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Tisagenlecleucel_monotherapy_99|Tisagenlecleucel]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS<br>Median EFS: 3 vs 3 mo<br>(HR 0.93, 95% CI 0.71-1.22)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*NCIC-CTG LY.12: Previous treatment with one [[Regimen_classes#Anthracycline-based_regimen|anthracycline-containing chemotherapy regimen]]
 
−
*ZUMA-7: Failure of first-line chemoimmunotherapy including an [[Regimen_classes#Anti-CD20-based_regimen|anti-CD20 monoclonal antibody]] and an [[Regimen_classes#Anthracycline-based_regimen|anthracycline-containing regimen]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1 or day -1
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on day 2 (total dose per cycle: 4000 mg/m<sup>2</sup>)
 
−
*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
 
−
'''21-day cycle for up to 3 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Responders: Stem-cell mobilization and [[Regimen_classes#High-dose_chemotherapy_with_auto_HSCT|high-dose chemotherapy with autologous hematopoietic stem cell transplant (regimen not specified)]]
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3 {{#subobject:65859a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1080/07357900600814490 Mey et al. 2006]
 
−
|NR in abstract
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''The doses here were used after a mid-protocol amendment pertaining to the first cycle, and are intended for patients younger than 60 years of age.''
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycle 1: 40 mg PO once per day on days 3 to 5
 
−
**Cycles 2 to 4: 40 mg PO once per day on days 3 to 6
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] as follows:
 
−
**Cycle 1: 1000 mg/m<sup>2</sup> IV over 2 hours every 12 hours on day 4 (total dose per cycle: 2000 mg/m<sup>2</sup>)
 
−
**Cycles 2 to 4: 2000 mg/m<sup>2</sup> IV over 2 hours every 12 hours on day 4 (total dose per cycle: 4000 mg/m<sup>2</sup>)
 
−
*[[Cisplatin (Platinol)]] as follows:
 
−
**Cycle 1: 25 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 3 (total dose: 75 mg/m<sup>2</sup>)
 
−
**Cycles 2 to 4: 25 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 3 (total dose per cycle: 100 mg/m<sup>2</sup>)
 
−
'''21-day cycle for up to 4 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients with at least PR were allowed to undergo high-dose chemotherapy with autologous stem-cell transplant (regimen not specified)
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3 {{#subobject:65859a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1080/07357900600814490 Mey et al. 2006]
 
−
|NR in abstract
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''The doses here were used after a mid-protocol amendment pertaining to the first cycle, and are intended for patients older than 60 years of age.''
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycle 1: 40 mg PO once per day on days 3 to 5
 
−
**Cycles 2 to 4: 40 mg PO once per day on days 3 to 6
 
−
====Chemotherapy====
 
−
*[[Cytarabine (Ara-C)]] as follows:
 
−
**Cycle 1: 500 mg/m<sup>2</sup> IV over 2 hours every 12 hours on day 4 (total dose per cycle: 1000 mg/m<sup>2</sup>)
 
−
**Cycles 2 to 4: 1000 mg/m<sup>2</sup> IV over 2 hours every 12 hours on day 4 (total dose per cycle: 2000 mg/m<sup>2</sup>)
 
−
*[[Cisplatin (Platinol)]] as follows:
 
−
**Cycle 1: 25 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 3 (total dose: 75 mg/m<sup>2</sup>)
 
−
**Cycles 2 to 4: 25 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 3 (total dose per cycle: 100 mg/m<sup>2</sup>)
 
−
'''21-day cycle for up to 4 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients with at least PR were allowed to undergo high-dose chemotherapy with autologous stem-cell transplant (regimen not specified)
 
−
</div></div>
 
−
===References===
 
−
#Mey UJ, Orlopp KS, Flieger D, Strehl JW, Ho AD, Hensel M, Bopp C, Gorschlüter M, Wilhelm M, Birkmann J, Kaiser U, Neubauer A, Florschütz A, Rabe C, Hahn C, Glasmacher AG, Schmidt-Wolf IG. Dexamethasone, high-dose cytarabine, and cisplatin in combination with rituximab as salvage treatment for patients with relapsed or refractory aggressive non-Hodgkin's lymphoma. Cancer Invest. 2006 Oct;24(6):593-600. [https://doi.org/10.1080/07357900600814490 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16982464 PubMed]
 
−
<!-- # Hagberg H, Gisselbrecht C; CORAL study group. Randomised phase III study of R-ICE versus R-DHAP in relapsed patients with CD20 diffuse large B-cell lymphoma (DLBCL) followed by high-dose therapy and a second randomisation to maintenance treatment with rituximab or not: an update of the CORAL study. Ann Oncol. 2006 May;17 Suppl 4:iv31-2. [http://annonc.oxfordjournals.org/content/17/suppl_4/iv31.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/16702182 PubMed]
 
−
# Presented at the 45th Annual Meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL, and at the 51st Annual Meeting of the American Society of Hematology, December 5-8, 2009, New Orleans, LA. -->
 
−
#'''CORAL:''' Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Brière J, Moskowitz CH, Schmitz N. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010 Sep 20;28(27):4184-90. Epub 2010 Jul 26. Erratum in: J Clin Oncol. 2012 May 20;30(15):1896. [https://doi.org/10.1200/jco.2010.28.1618 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664033/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20660832 PubMed] NCT00137995
 
−
<!-- Presented in part at the Annual Meeting of the American Society of Hematology, Atlanta, GA, December 7-10, 2013, and the International Conference on Malignant Lymphoma, Lugano, Switzerland, June 19-22, 2013. -->
 
−
#'''NCIC-CTG LY.12:''' Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. Epub 2014 Sep 29. [https://doi.org/10.1200/jco.2013.53.9593 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25267740 PubMed] NCT00078949
 
−
#'''ORCHARRD:''' van Imhoff GW, McMillan A, Matasar MJ, Radford J, Ardeshna KM, Kuliczkowski K, Kim W, Hong X, Goerloev JS, Davies A, Barrigón MD, Ogura M, Leppä S, Fennessy M, Liao Q, van der Holt B, Lisby S, Hagenbeek A. Ofatumumab versus rituximab salvage chemoimmunotherapy in relapsed or refractory diffuse large B-cell lymphoma: the ORCHARRD study. J Clin Oncol. 2017 Feb 10;35(5):544-51. Epub 2016 Dec 28. [https://doi.org/10.1200/JCO.2016.69.0198 link to original article] [https://ascopubs.org/doi/suppl/10.1200/JCO.2016.69.0198/suppl_file/ds_2016.690198.pdf link to data supplement] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28029326 PubMed] NCT01014208
 
−
#'''ZUMA-7:''' Locke FL, Miklos DB, Jacobson CA, Perales MA, Kersten MJ, Oluwole OO, Ghobadi A, Rapoport AP, McGuirk J, Pagel JM, Muñoz J, Farooq U, van Meerten T, Reagan PM, Sureda A, Flinn IW, Vandenberghe P, Song KW, Dickinson M, Minnema MC, Riedell PA, Leslie LA, Chaganti S, Yang Y, Filosto S, Shah J, Schupp M, To C, Cheng P, Gordon LI, Westin JR; All ZUMA-7 Investigators and Contributing Kite Members. Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma. N Engl J Med. 2022 Feb 17;386(7):640-654. Epub 2021 Dec 11. [https://doi.org/10.1056/nejmoa2116133 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/34891224/ PubMed] NCT03391466
 
−
#'''BELINDA:''' Bishop MR, Dickinson M, Purtill D, Barba P, Santoro A, Hamad N, Kato K, Sureda A, Greil R, Thieblemont C, Morschhauser F, Janz M, Flinn I, Rabitsch W, Kwong YL, Kersten MJ, Minnema MC, Holte H, Chan EHL, Martinez-Lopez J, Müller AMS, Maziarz RT, McGuirk JP, Bachy E, Le Gouill S, Dreyling M, Harigae H, Bond D, Andreadis C, McSweeney P, Kharfan-Dabaja M, Newsome S, Degtyarev E, Awasthi R, Del Corral C, Andreola G, Masood A, Schuster SJ, Jäger U, Borchmann P, Westin JR. Second-Line Tisagenlecleucel or Standard Care in Aggressive B-Cell Lymphoma. N Engl J Med. 2022 Feb 17;386(7):629-639. Epub 2021 Dec 14. [https://doi.org/10.1056/nejmoa2116596 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/34904798/ PubMed] NCT03570892
 
−
==R-DHAP/R-VIM {{#subobject:e57948|Regimen=1}}==
 
−
R-DHAP/R-VIM: '''<u>R</u>'''ituximab, '''<u>D</u>'''examethasone, '''<u>H</u>'''igh-dose '''<u>A</u>'''ra-C (Cytarabine), '''<u>P</u>'''latinol (Cisplatin) alternating with '''<u>R</u>'''ituximab, '''<u>V</u>'''P-16 (Etoposide), '''<u>I</u>'''fosfamide, '''<u>M</u>'''ethotrexate
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:f46b7f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/111/2/537.long Vellenga et al. 2008 (HOVON-44)]
 
−
|2000-2005
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#DHAP.2FVIM_88|DHAP/VIM]]
 
−
| style="background-color:#1a9850" |Superior PFS
 
−
|-
 
−
|}
 
−
''Note: per the paper, "in case patients were non-responsive to R-DHAP but responsive to R-VIM, it was allowed to repeat the R-VIM regimen as the third cycle of reinduction chemotherapy." No statement is made as to whether Mesna is used in the VIM protocol.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy, R-DHAP portion====
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycles 1 & 3: 375 mg/m<sup>2</sup> IV once on day 5
 
−
====Glucocorticoid therapy, R-DHAP portion====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 1 & 3: 40 mg IV or PO once per day on days 1 to 4
 
−
====Chemotherapy, R-DHAP portion====
 
−
*[[Cytarabine (Ara-C)]] as follows:
 
−
**Cycles 1 & 3: 2000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on day 2 (total dose per cycle: 4000 mg/m<sup>2</sup>)
 
−
*[[Cisplatin (Platinol)]] as follows:
 
−
**Cycles 1 & 3: 100 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
 
−
====Targeted therapy, R-VIM portion====
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 2: 375 mg/m<sup>2</sup> IV once on day 6
 
−
====Chemotherapy, R-VIM portion====
 
−
*[[Etoposide (Vepesid)]] as follows:
 
−
**Cycle 2: 90 mg/m<sup>2</sup> IV once per day on days 1, 3, 5
 
−
*[[Ifosfamide (Ifex)]] as follows:
 
−
**Cycle 2: 1200 mg/m<sup>2</sup> IV once per day on days 1 to 5
 
−
*[[Methotrexate (MTX)]] as follows:
 
−
**Cycle 2: 30 mg/m<sup>2</sup> IV once per day on days 1 & 5
 
−
'''28-day cycle for 3 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Responders: Stem-cell mobilization, then [[#BEAM.2C_then_auto_HSCT|BEAM with autologous hematopoietic stem cell transplant]]
 
−
</div></div>
 
−
===References===
 
−
#'''HOVON-44:''' Vellenga E, van Putten WL, van 't Veer MB, Zijlstra JM, Fibbe WE, van Oers MH, Verdonck LF, Wijermans PW, van Imhoff GW, Lugtenburg PJ, Huijgens PC. Rituximab improves the treatment results of DHAP-VIM-DHAP and ASCT in relapsed/progressive aggressive CD20+ NHL: a prospective randomized HOVON trial. Blood. 2008 Jan 15;111(2):537-43. [http://www.bloodjournal.org/content/111/2/537.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17971487 PubMed] NCT00012051
 
−
==R-EPOCH {{#subobject:ddfe7d|Regimen=1}}==
 
−
R-EPOCH: '''<u>R</u>'''ituximab, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>O</u>'''ncovin (Vincristine), '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:a10d44|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdh093 Jermann et al. 2004]
 
−
|1998-2001
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Note: this is not the dose-adjusted R-EPOCH regimen''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Etoposide (Vepesid)]] 65 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 2 (total dose per cycle: 195 mg/m<sup>2</sup>)
 
−
*[[Vincristine (Oncovin)]] 0.5 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 2 (total dose per cycle: 1.5 mg/m<sup>2</sup>)
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 5
 
−
*[[Doxorubicin (Adriamycin)]] 15 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 2 (total dose per cycle: 45 mg/m<sup>2</sup>)
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day PO on days 1 to 14
 
−
'''21-day cycle for 4 to 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Patients younger than 60 who achieved at least PR: [[Regimen_classes#High-dose_chemotherapy_with_auto_HSCT|High-dose chemotherapy with autologous hematopoietic stem-cell transplantation (regimen not specified)]]
 
−
</div></div>
 
−
===References===
 
−
#Jermann M, Jost LM, Taverna Ch, Jacky E, Honegger HP, Betticher DC, Egli F, Kroner T, Stahel RA. Rituximab-EPOCH, an effective salvage therapy for relapsed, refractory or transformed B-cell lymphomas: results of a phase II study. Ann Oncol. 2004 Mar;15(3):511-6. [https://doi.org/10.1093/annonc/mdh093 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14998858 PubMed]
 
−
==R-ESHAP {{#subobject:7794d|Regimen=1}}==
 
−
R-ESHAP: '''<u>R</u>'''ituximab, '''<u>E</u>'''toposide, '''<u>S</u>'''olumedrol (Methylprednisolone) '''<u>H</u>'''igh-dose '''<u>A</u>'''ra-C (Cytarabine), '''<u>P</u>'''latinol (Cisplatin)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:b6038c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.haematologica.org/content/93/12/1829.long Martín et al. 2008]
 
−
|2000-2007
 
−
| style="background-color:#ffffbe" |Retrospective
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(11)70097-0 Avilés et al. 2010]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#ESHAP|ESHAP]]
 
−
| style="background-color:#ffffbf" |Did not meet efficacy endpoints
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa2116133 Locke et al. 2021 (ZUMA-7)]
 
−
|2018-2019
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Axicabtagene_ciloleucel_monotherapy|Axicabtagene ciloleucel]]
 
−
| style="background-color:#d73027" |Inferior EFS
 
−
|-
 
−
|}
 
−
''Regimen details are based on the ZUMA-7 protocol, which makes reference to Martin et al. 2008.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*ZUMA-7: Failure of first-line chemoimmunotherapy including an [[Regimen_classes#Anti-CD20-based_regimen|anti-CD20 monoclonal antibody]] and an [[Regimen_classes#Anthracycline-based_regimen|anthracycline-containing regimen]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Etoposide (Vepesid)]] 40 mg/m<sup>2</sup> IV once per day on days 1 to 4
 
−
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV once on day 5
 
−
*[[Cisplatin (Platinol)]] 25 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 100 mg/m<sup>2</sup>)
 
−
====Glucocorticoid therapy====
 
−
*[[Methylprednisolone (Solumedrol)]] 500 mg IV once per day on days 1 to 4 or 1 to 5
 
−
</div></div>
 
−
===References===
 
−
#'''Retrospective:''' Martín A, Conde E, Arnan M, Canales MA, Deben G, Sancho JM, Andreu R, Salar A, García-Sanchez P, Vázquez L, Nistal S, Requena MJ, Donato EM, González JA, León A, Ruiz C, Grande C, González-Barca E, Caballero MD; Grupo Español de Linfomas/Trasplante Autólogo de Médula Osea. R-ESHAP as salvage therapy for patients with relapsed or refractory diffuse large B-cell lymphoma: the influence of prior exposure to rituximab on outcome. A GEL/TAMO study. Haematologica. 2008 Dec;93(12):1829-36. Epub 2008 Oct 22. [http://www.haematologica.org/content/93/12/1829.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18945747 PubMed]
 
−
#Avilés A, Neri N, Huerta-Guzmán J, de Jesús Nambo M. ESHAP versus rituximab-ESHAP in frail patients with refractory diffuse large B-cell lymphoma. Clin Lymphoma Myeloma Leuk. 2010 Apr;10(2):125-8. [http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(11)70097-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20371445 PubMed]
 
−
#'''ZUMA-7:''' Locke FL, Miklos DB, Jacobson CA, Perales MA, Kersten MJ, Oluwole OO, Ghobadi A, Rapoport AP, McGuirk J, Pagel JM, Muñoz J, Farooq U, van Meerten T, Reagan PM, Sureda A, Flinn IW, Vandenberghe P, Song KW, Dickinson M, Minnema MC, Riedell PA, Leslie LA, Chaganti S, Yang Y, Filosto S, Shah J, Schupp M, To C, Cheng P, Gordon LI, Westin JR; All ZUMA-7 Investigators and Contributing Kite Members. Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma. N Engl J Med. 2022 Feb 17;386(7):640-654. Epub 2021 Dec 11. [https://doi.org/10.1056/nejmoa2116133 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/34891224/ PubMed] NCT03391466
 
−
==R-GDP {{#subobject:a5d411|Regimen=1}}==
 
−
R-GDP: '''<u>R</u>'''ituximab, '''<u>G</u>'''emcitabine, '''<u>D</u>'''examethasone, '''<u>P</u>'''latinol (Cisplatin)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 1 day of cisplatin/cycle {{#subobject:c6480d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2013.53.9593 Crump et al. 2014 (NCIC-CTG LY.12)]
 
−
|2003-2011
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#R-DHAP|R-DHAP]]
 
−
| style="background-color:#eeee01" |Non-inferior RR after 2 cycles
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa2116133 Locke et al. 2021 (ZUMA-7)]
 
−
|2018-2019
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Axicabtagene_ciloleucel_monotherapy|Axicabtagene ciloleucel]]
 
−
| style="background-color:#d73027" |Inferior EFS
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa2116596 Bishop et al. 2021 (BELINDA)]
 
−
|2019-2021
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Tisagenlecleucel_monotherapy_99|Tisagenlecleucel]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS<br>Median EFS: 3 vs 3 mo<br>(HR 0.93, 95% CI 0.71-1.22)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*NCIC-CTG LY.12: Previous treatment with one [[Regimen_classes#Anthracycline-based_regimen|anthracycline-containing chemotherapy regimen]]
 
−
*ZUMA-7: Failure of first-line chemoimmunotherapy including an [[Regimen_classes#Anti-CD20-based_regimen|anti-CD20 monoclonal antibody]] and an [[Regimen_classes#Anthracycline-based_regimen|anthracycline-containing regimen]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 
−
'''21-day cycle for up to 3 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Responders: Stem-cell mobilization and [[Regimen_classes#High-dose_chemotherapy_with_auto_HSCT|high-dose chemotherapy with autologous hematopoietic stem cell transplant (regimen not specified)]]
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 3 days of cisplatin/cycle {{#subobject:325d38|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://link.springer.com/article/10.1007/s12032-012-0211-2 Hou et al. 2012]
 
−
|2005-2010
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Cisplatin (Platinol)]] 25 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
====Glucocorticoid therapy====
 
−
*[[Dexamethasone (Decadron)]] 40 mg IV once per day on days 1 to 4
 
−
'''21-day cycle for up to 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#Hou Y, Wang HQ, Ba Y. Rituximab, gemcitabine, cisplatin, and dexamethasone in patients with refractory or relapsed aggressive B-cell lymphoma. Med Oncol. 2012 Dec;29(4):2409-16. Epub 2012 Apr 3. [http://link.springer.com/article/10.1007/s12032-012-0211-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22476761 PubMed]
 
−
#'''NCIC-CTG LY.12:''' Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. Epub 2014 Sep 29. [https://doi.org/10.1200/jco.2013.53.9593 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25267740 PubMed] NCT00078949
 
−
#'''ZUMA-7:''' Locke FL, Miklos DB, Jacobson CA, Perales MA, Kersten MJ, Oluwole OO, Ghobadi A, Rapoport AP, McGuirk J, Pagel JM, Muñoz J, Farooq U, van Meerten T, Reagan PM, Sureda A, Flinn IW, Vandenberghe P, Song KW, Dickinson M, Minnema MC, Riedell PA, Leslie LA, Chaganti S, Yang Y, Filosto S, Shah J, Schupp M, To C, Cheng P, Gordon LI, Westin JR; All ZUMA-7 Investigators and Contributing Kite Members. Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma. N Engl J Med. 2022 Feb 17;386(7):640-654. Epub 2021 Dec 11. [https://doi.org/10.1056/nejmoa2116133 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/34891224/ PubMed] NCT03391466
 
−
#'''BELINDA:''' Bishop MR, Dickinson M, Purtill D, Barba P, Santoro A, Hamad N, Kato K, Sureda A, Greil R, Thieblemont C, Morschhauser F, Janz M, Flinn I, Rabitsch W, Kwong YL, Kersten MJ, Minnema MC, Holte H, Chan EHL, Martinez-Lopez J, Müller AMS, Maziarz RT, McGuirk JP, Bachy E, Le Gouill S, Dreyling M, Harigae H, Bond D, Andreadis C, McSweeney P, Kharfan-Dabaja M, Newsome S, Degtyarev E, Awasthi R, Del Corral C, Andreola G, Masood A, Schuster SJ, Jäger U, Borchmann P, Westin JR. Second-Line Tisagenlecleucel or Standard Care in Aggressive B-Cell Lymphoma. N Engl J Med. 2022 Feb 17;386(7):629-639. Epub 2021 Dec 14. [https://doi.org/10.1056/nejmoa2116596 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/34904798/ PubMed] NCT03570892
 
−
==R-GemOx {{#subobject:agbc11|Regimen=1}}==
 
−
R-GemOx: '''<u>R</u>'''ituximab, '''<u>Gem</u>'''citabine, '''<u>Ox</u>'''aliplatin
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:jbp0d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa2116596 Bishop et al. 2021 (BELINDA)]
 
−
|2019-2021
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Tisagenlecleucel_monotherapy_99|Tisagenlecleucel]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS<br>Median EFS: 3 vs 3 mo<br>(HR 0.93, 95% CI 0.71-1.22)
 
−
|-
 
−
|}
 
−
''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm in this setting.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once on day 2
 
−
*[[Oxaliplatin (Eloxatin)]] 100 mg/m<sup>2</sup> IV once on day 1
 
−
'''15-day cycle for 2 or more cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Responders: Stem-cell mobilization and [[Regimen_classes#High-dose_chemotherapy_with_auto_HSCT|high-dose chemotherapy with autologous hematopoietic stem cell transplant (BEAM preferred)]]
 
−
</div></div>
 
−
===References===
 
−
#'''BELINDA:''' Bishop MR, Dickinson M, Purtill D, Barba P, Santoro A, Hamad N, Kato K, Sureda A, Greil R, Thieblemont C, Morschhauser F, Janz M, Flinn I, Rabitsch W, Kwong YL, Kersten MJ, Minnema MC, Holte H, Chan EHL, Martinez-Lopez J, Müller AMS, Maziarz RT, McGuirk JP, Bachy E, Le Gouill S, Dreyling M, Harigae H, Bond D, Andreadis C, McSweeney P, Kharfan-Dabaja M, Newsome S, Degtyarev E, Awasthi R, Del Corral C, Andreola G, Masood A, Schuster SJ, Jäger U, Borchmann P, Westin JR. Second-Line Tisagenlecleucel or Standard Care in Aggressive B-Cell Lymphoma. N Engl J Med. 2022 Feb 17;386(7):629-639. Epub 2021 Dec 14. [https://doi.org/10.1056/nejmoa2116596 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/34904798/ PubMed] NCT03570892
 
−
==R-ICE {{#subobject:117cd8|Regimen=1}}==
 
−
R-ICE: '''<u>R</u>'''ituximab, '''<u>I</u>'''fosfamide, '''<u>C</u>'''arboplatin, '''<u>E</u>'''toposide
 
−
<br>ICE-R: '''<u>I</u>'''fosfamide, '''<u>C</u>'''arboplatin, '''<u>E</u>'''toposide, '''<u>R</u>'''ituximab
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1 {{#subobject:35e1ac|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664033/ Gisselbrecht et al. 2010 (CORAL)]
 
−
|2003-2007
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#R-DHAP|R-DHAP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of mobilization-adjusted response rate after 3 cycles
 
−
|-
 
−
|[http://www.tandfonline.com/doi/full/10.3109/10428194.2015.1007504 Fayad et al. 2015 (SG040-0005)]
 
−
|2007-2009
 
−
| style="background-color:#1a9851" |Randomized Phase 2b (C)
 
−
|[[#R-ICE_.26_Dacetuzumab_77|R-ICE & Dacetuzumab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of CR rate
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa2116133 Locke et al. 2021 (ZUMA-7)]
 
−
|2018-2019
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Axicabtagene_ciloleucel_monotherapy|Axicabtagene ciloleucel]]
 
−
| style="background-color:#d73027" |Inferior EFS
 
−
|-
 
−
|[https://doi.org/10.1056/nejmoa2116596 Bishop et al. 2021 (BELINDA)]
 
−
|2019-2021
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Tisagenlecleucel_monotherapy_99|Tisagenlecleucel]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS<br>Median EFS: 3 vs 3 mo<br>(HR 0.93, 95% CI 0.71-1.22)
 
−
|-
 
−
</div></div><br>
 
−
|}
 
−
''Note: Gisselbrecht et al. 2010 refers to the non-randomized regimen described in variant #3 below, although it has slightly different day numbering. Doses are the same. ZUMA-7 & BELINDA describe just one dose of rituximab per cycle, given on the day prior to chemotherapy.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*ZUMA-7: Failure of first-line chemoimmunotherapy including an [[Regimen_classes#Anti-CD20-based_regimen|anti-CD20 monoclonal antibody]] and an [[Regimen_classes#Anthracycline-based_regimen|anthracycline-containing regimen]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] as follows (given first before other chemotherapy; see note):
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days -1 & 1
 
−
**Cycles 2 & 3: 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Ifosfamide (Ifex)]] 5000 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 2
 
−
*[[Carboplatin (Paraplatin)]] AUC 5 (maximum dose of 800 mg) IV once on day 2
 
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
====Supportive therapy====
 
−
*[[Mesna (Mesnex)]] given with [[Ifosfamide (Ifex)]] (dose & schedule not specified)
 
−
*"[[Filgrastim (Neupogen) | Granulocyte colony-stimulating factor]] was administered after R-ICE"
 
−
'''21-day cycle for 2 to 3 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Complete or partial response: [[#BEAM.2C_then_auto_HSCT|BEAM with autologous hematopoietic stem cell transplant]]
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2 {{#subobject:871cdf|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
! style="width: 33%" |Study
 
−
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[http://zhxyxzz.yiigle.com/zhxyxzz20143504/395338.htm Guo et al. 2014]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#e0ecf4" |ORR: 78%
 
−
|-
 
−
|}
 
−
''Note: original article is in Chinese; this information is from the English abstract.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Ifosfamide (Ifex)]] 1600 mg/m<sup>2</sup> IV once per day on days 2 to 4
 
−
*[[Carboplatin (Paraplatin)]] AUC 5 (maximum dose of 800 mg) IV once on day 3
 
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 2 to 4
 
−
'''3 cycles; duration of cycles not specified in the abstract'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3 {{#subobject:820b17|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdg702 Zelenetz et al. 2003]
 
−
|1993-2000
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#e0ecf4" |ORR: 81%
 
−
|-
 
−
|[http://www.bloodjournal.org/content/103/10/3684.long Kewalramani et al. 2004]
 
−
|NR in abstract
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#e0ecf4" |ORR: 78%
 
−
|-
 
−
|}
 
−
''Third cycle intended to be followed by peripheral blood hematopoietic stem cell collection. ORR reported in Zelenetz et al. 2003 is for the subset of DLBCL patients who received R-ICE; it is unclear if these patients were exposed to rituximab previously. None of the patients in Kewalaramani et al. 2004 had previously received rituximab.''
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days -2 & 1
 
−
**Cycles 2 & 3: 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Ifosfamide (Ifex)]] 5000 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 4, '''mixed with mesna'''
 
−
*[[Carboplatin (Paraplatin)]] AUC 5 (maximum dose of 800 mg) IV bolus once on day 4
 
−
**Carboplatin AUC calculated based on a 12-hour creatinine clearance
 
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV bolus once per day on days 3 to 5
 
−
====Supportive therapy====
 
−
*(as described by Kewalramani et al. 2004):
 
−
*[[Mesna (Mesnex)]] 5000 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 4, '''mixed with [[Ifosfamide (Ifex)]]'''
 
−
*[[Acetaminophen (Tylenol)]] 650 mg PO once as premedication for [[Rituximab (Rituxan)]]
 
−
*[[Diphenhydramine (Benadryl)]] 50 mg IV once as premedication for [[Rituximab (Rituxan)]]
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on days 7 to 14 (10 mcg/kg with cycle 3, given until collection of peripheral blood hematopoietic stem cells)
 
−
'''14-day cycle for 3 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#Zelenetz AD, Hamlin P, Kewalramani T, Yahalom J, Nimer S, Moskowitz CH. Ifosfamide, carboplatin, etoposide (ICE)-based second-line chemotherapy for the management of relapsed and refractory aggressive non-Hodgkin's lymphoma. Ann Oncol. 2003;14 Suppl 1:i5-10. [https://doi.org/10.1093/annonc/mdg702 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12736224 PubMed]
 
−
#Kewalramani T, Zelenetz AD, Nimer SD, Portlock C, Straus D, Noy A, O'Connor O, Filippa DA, Teruya-Feldstein J, Gencarelli A, Qin J, Waxman A, Yahalom J, Moskowitz CH. Rituximab and ICE as second-line therapy before autologous stem cell transplantation for relapsed or primary refractory diffuse large B-cell lymphoma. Blood. 2004 May 15;103(10):3684-8. Epub 2004 Jan 22. [http://www.bloodjournal.org/content/103/10/3684.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/14739217 PubMed]
 
−
<!-- # Hagberg H, Gisselbrecht C; CORAL study group. Randomised phase III study of R-ICE versus R-DHAP in relapsed patients with CD20 diffuse large B-cell lymphoma (DLBCL) followed by high-dose therapy and a second randomisation to maintenance treatment with rituximab or not: an update of the CORAL study. Ann Oncol. 2006 May;17 Suppl 4:iv31-2. [http://annonc.oxfordjournals.org/content/17/suppl_4/iv31.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/16702182 PubMed]
 
−
Presented at the 45th Annual Meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL, and at the 51st Annual Meeting of the American Society of Hematology, December 5-8, 2009, New Orleans, LA. -->
 
−
#'''CORAL:''' Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Brière J, Moskowitz CH, Schmitz N. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010 Sep 20;28(27):4184-90. Epub 2010 Jul 26. Erratum in: J Clin Oncol. 2012 May 20;30(15):1896. [https://doi.org/10.1200/jco.2010.28.1618 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664033/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20660832 PubMed] NCT00137995
 
−
#Guo Y, Chen Y, Hong X, Yu L, Ma J, Shi Y, Liu T, Jiang W, Zhu J, Jin J, Zou P, Wu D, Shen Z. [A phase II multicenter study to investigate R-ICE as a salvage therapy for relapsed diffuse large B-cell lymphoma]. Zhonghua Xue Ye Xue Za Zhi. 2014 Apr;35(4):314-7. Chinese. [http://zhxyxzz.yiigle.com/zhxyxzz20143504/395338.htm link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/24759019 PubMed]
 
−
#'''SG040-0005:''' Fayad L, Ansell SM, Advani R, Coiffier B, Stuart R, Bartlett NL, Forero-Torres A, Kuliczkowski K, Belada D, Ng E, Drachman JG. Dacetuzumab plus rituximab, ifosfamide, carboplatin and etoposide as salvage therapy for patients with diffuse large B-cell lymphoma relapsing after rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone: a randomized, double-blind, placebo-controlled phase 2b trial. Leuk Lymphoma. 2015;56(9):2569-78. Epub 2015 Feb 26. [http://www.tandfonline.com/doi/full/10.3109/10428194.2015.1007504 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25651427 PubMed] NCT00529503
 
−
#'''ZUMA-7:''' Locke FL, Miklos DB, Jacobson CA, Perales MA, Kersten MJ, Oluwole OO, Ghobadi A, Rapoport AP, McGuirk J, Pagel JM, Muñoz J, Farooq U, van Meerten T, Reagan PM, Sureda A, Flinn IW, Vandenberghe P, Song KW, Dickinson M, Minnema MC, Riedell PA, Leslie LA, Chaganti S, Yang Y, Filosto S, Shah J, Schupp M, To C, Cheng P, Gordon LI, Westin JR; All ZUMA-7 Investigators and Contributing Kite Members. Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma. N Engl J Med. 2022 Feb 17;386(7):640-654. Epub 2021 Dec 11. [https://doi.org/10.1056/nejmoa2116133 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/34891224/ PubMed] NCT03391466
 
−
#'''BELINDA:''' Bishop MR, Dickinson M, Purtill D, Barba P, Santoro A, Hamad N, Kato K, Sureda A, Greil R, Thieblemont C, Morschhauser F, Janz M, Flinn I, Rabitsch W, Kwong YL, Kersten MJ, Minnema MC, Holte H, Chan EHL, Martinez-Lopez J, Müller AMS, Maziarz RT, McGuirk JP, Bachy E, Le Gouill S, Dreyling M, Harigae H, Bond D, Andreadis C, McSweeney P, Kharfan-Dabaja M, Newsome S, Degtyarev E, Awasthi R, Del Corral C, Andreola G, Masood A, Schuster SJ, Jäger U, Borchmann P, Westin JR. Second-Line Tisagenlecleucel or Standard Care in Aggressive B-Cell Lymphoma. N Engl J Med. 2022 Feb 17;386(7):629-639. Epub 2021 Dec 14. [https://doi.org/10.1056/nejmoa2116596 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/34904798/ PubMed] NCT03570892
 
−
==RICER {{#subobject:28fda|Regimen=1}}==
 
−
RICER: '''<u>R</u>'''ituximab, '''<u>I</u>'''fosfamide, '''<u>C</u>'''arboplatin, '''<u>E</u>'''toposide, '''<u>R</u>'''evlimid (Lenalidomide)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:f8dffd|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4283736/ Feldman et al. 2014 (RV-DLBCL-PI-0463)]
 
−
|2010-2012
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 7
 
−
====Chemotherapy====
 
−
*[[Ifosfamide (Ifex)]] 5000 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 2, '''mixed with mesna'''
 
−
*[[Carboplatin (Paraplatin)]] AUC 5 (maximum dose of 800 mg) IV once on day 2
 
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV bolus once per day on days 2 to 4
 
−
====Supportive therapy====
 
−
*[[Mesna (Mesnex)]] 5000 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 2, '''mixed with [[Ifosfamide (Ifex)]]'''
 
−
*[[Aspirin]] 81 mg PO once per day from day 1 until platelets less than 50 × 10<sup>9</sup>/L
 
−
*Low dose LMWH for patients intolerant of [[Aspirin]]
 
−
*"[[Filgrastim (Neupogen) | Granulocyte colony-stimulating factor]] was administered after R-ICE"
 
−
'''14-day cycle for 2 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Responders received a 3rd cycle with hematopoietic stem cell collection 10 to 14 days afterwards, then [[#BEAM.2C_then_auto_HSCT|BEAM with autologous hematopoietic stem cell transplant (details not described)]]
 
−
</div></div>
 
−
===References===
 
−
#'''RV-DLBCL-PI-0463:''' Feldman T, Mato AR, Chow KF, Protomastro EA, Yannotti KM, Bhattacharyya P, Yang X, Donato ML, Rowley SD, Carini C, Valentinetti M, Smith J, Gadaleta G, Bejot C, Stives S, Timberg M, Kdiry S, Pecora AL, Beaven AW, Goy A. Addition of lenalidomide to rituximab, ifosfamide, carboplatin, etoposide (RICER) in first-relapse/primary refractory diffuse large B-cell lymphoma. Br J Haematol. 2014 Jul;166(1):77-83. Epub 2014 Mar 25. [https://doi.org/10.1111/bjh.12846 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4283736/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24661044 PubMed] NCT01241734
 
−
==R-IFE {{#subobject:19b4ea|Regimen=1}}==
 
−
R-IFE: '''<u>R</u>'''ituximab, '''<u>IF</u>'''osfamide, '''<u>E</u>'''toposide
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:116aa7|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.13036 Pardal et al. 2014 (GELTAMO-2006)]
 
−
|2007-2009
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''These were patients with PET-positive disease at interim assessment.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#R-MegaCHOP|R-MegaCHOP]] x 3
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Ifosfamide (Ifex)]] 3333 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 1 (total dose per cycle: 10,000 mg/m<sup>2</sup>)
 
−
*[[Etoposide (Vepesid)]] 150 mg/m<sup>2</sup> IV over 12 hours once per day on days 1 to 3
 
−
====Supportive therapy====
 
−
*[[Mesna (Mesnex)]] given after R-IFE; details not supplied in manuscript
 
−
*[[Pegfilgrastim (Neulasta)]] given after each cycle
 
−
'''2 cycles (duration not specified)'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Responders: [[#BEAM.2C_then_auto_HSCT|BEAM with autologous hematopoietic stem cell transplant]]
 
−
</div></div>
 
−
===References===
 
−
#'''GELTAMO-2006:''' Pardal E, Coronado M, Martín A, Grande C, Marín-Niebla A, Panizo C, Bello JL, Conde E, Hernández MT, Arranz R, Bargay J, González-Barca E, Pérez-Ceballos E, Montes-Moreno S, Caballero MD. Intensification treatment based on early FDG-PET in patients with high-risk diffuse large B-cell lymphoma: a phase II GELTAMO trial. Br J Haematol. 2014 Nov;167(3):327-36. Epub 2014 Jul 28. [https://doi.org/10.1111/bjh.13036 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25066542 PubMed] NCT013611091
 
−
==R-NIMP {{#subobject:fb6d8|Regimen=1}}==
 
−
R-NIMP: '''<u>R</u>'''ituximab, '''<u>N</u>'''avelbine (Vinorelbine), '''<u>I</u>'''fosfamide, '''<u>M</u>'''itoxantrone, '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:8fecee|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.12379 Gyan et al. 2013]
 
−
|2004-2010
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|68% (95% CI: 53–79)
 
−
|-
 
−
|}
 
−
''BSA was capped at 2 for all dose calculations.''
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Vinorelbine (Navelbine)]] 25 mg/m<sup>2</sup> IV once per day on days 1 & 15
 
−
*[[Ifosfamide (Ifex)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 5000 mg/m<sup>2</sup>)
 
−
*[[Mitoxantrone (Novantrone)]] 10 mg/m<sup>2</sup> IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 1 mg/kg (route not specified) once per day on days 1 to 5
 
−
====Supportive therapy====
 
−
*[[Mesna (Mesnex)]] given with [[Ifosfamide (Ifex)]] "at the same dose"; schedule not specified in the paper
 
−
*Recommended: [[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 7
 
−
*Recommended: Epoietin alpha support for hemoglobin less than 10 g/dL
 
−
'''28-day cycle for 3 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Responders were recommended to undergo 3 additional cycles of R-NIMP (if transplant ineligible) or [[Regimen_classes#High-dose_chemotherapy_with_auto_HSCT|high-dose chemotherapy with autologous hematopoietic stem cell transplant (regimen not specified)]]
 
−
</div></div>
 
−
===References===
 
−
#Gyan E, Damotte D, Courby S, Sénécal D, Quittet P, Schmidt-Tanguy A, Banos A, Le Gouill S, Lamy T, Fontan J, Maisonneuve H, Alexis M, Dreyfus F, Tournilhac O, Laribi K, Solal-Céligny P, Arakelyan N, Cartron G, Gressin R; GOELAMS. High response rate and acceptable toxicity of a combination of rituximab, vinorelbine, ifosfamide, mitoxantrone and prednisone for the treatment of diffuse large B-cell lymphoma in first relapse: results of the R-NIMP GOELAMS study. Br J Haematol. 2013 Jul;162(2):240-9. Epub 2013 May 21. [https://doi.org/10.1111/bjh.12379 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23692641 PubMed]
 
−
=Consolidation after salvage therapy=
 
−
==BEAC, then auto HSCT {{#subobject:0341c3|Regimen=1}}==
 
−
BEAC: '''<u>R</u>'''ituximab, '''<u>B</u>'''iCNU (Carmustine), '''<u>E</u>'''toposide, '''<u>A</u>'''ra-C (Cytarabine), '''<u>C</u>'''yclophosphamide
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:61a3cd|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/77/7/1587.long Philip et al. 1991 (Parma)]
 
−
|1986-1987
 
−
| style="background-color:#91cf61" |Prospective pilot
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM199512073332305 Philip et al. 1995 (PARMA)]
 
−
|1987-1994
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#DHAP|DHAP]] x 4
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
[[Diffuse_large_B-cell_lymphoma_-_historical#DHAP|DHAP x 2]]; radiation was also given to sites of bulky disease (>5cm)
 
−
{{#lst:Autologous HSCT conditioning regimens|728b1c}}
 
−
</div></div>
 
−
===References===
 
−
#Philip T, Chauvin F, Armitage J, Bron D, Hagenbeek A, Biron P, Spitzer G, Velasquez W, Weisenburger DD, Fernandez-Ranada J, Somers R, Rizzoli V, Harousseau JL, Sotto JJ, Cahn JY, Guilhot F, Biggs J, Sonneveld P, Misset JL, Manna A, Jagannath S, Guglielmi C, Chevreau C, Delmer A, Santini G, Coiffier B. Parma international protocol: pilot study of DHAP followed by involved-field radiotherapy and BEAC with autologous bone marrow transplantation. Blood. 1991 Apr 1;77(7):1587-92. [http://www.bloodjournal.org/content/77/7/1587.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2009374 PubMed]
 
−
#'''PARMA:''' Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL, Coiffier B, Biron P, Mandelli F, Chauvin F. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med. 1995 Dec 7;333(23):1540-5. [https://doi.org/10.1056/NEJM199512073332305 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7477169 PubMed]
 
−
==BEAM, then allo HSCT {{#subobject:bda306|Regimen=1}}==
 
−
BEAM: '''<u>B</u>'''iCNU (Carmustine), '''<u>E</u>'''toposide, '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''elphalan
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:a8d4a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1093/oxfordjournals.annonc.a010369 Przepiorka et al. 1999]
 
−
|NR
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
{{#lst:Allogeneic HSCT|a8d4a}}
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Allogeneic stem cells]]
 
−
'''Stem cells transfused on day 0'''
 
−
</div></div>
 
−
===References===
 
−
#Przepiorka D, van Besien K, Khouri I, Hagemeister F, Samuels B, Folloder J, Ueno NT, Molldrem J, Mehra R, Körbling M, Giralt S, Gajewski J, Donato M, Cleary K, Claxton D, Braunschweig I, Andersson B, Anderlini P, Champlin R. Carmustine, etoposide, cytarabine and melphalan as a preparative regimen for allogeneic transplantation for high-risk malignant lymphoma. Ann Oncol. 1999 May;10(5):527-32. [https://doi.org/10.1093/oxfordjournals.annonc.a010369 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10416001 PubMed]
 
−
==BEAM, then auto HSCT {{#subobject:0304c6|Regimen=1}}==
 
−
BEAM: '''<u>R</u>'''ituximab, '''<u>B</u>'''iCNU (Carmustine), '''<u>E</u>'''toposide, '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''elphalan
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1 {{#subobject:445dc0|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1002/cncr.27418 Shimoni et al. 2012 (SHEBA-07-4466-AN-CTIL)]
 
−
|NR
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 
−
|[[#Z-BEAM.2C_then_auto_HSCT_2|Z-BEAM]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.13036 Pardal et al. 2014 (GELTAMO-2006)]
 
−
|2007-2009
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2016.69.0198 van Imhoff et al. 2016 (ORCHARRD)]
 
−
|2010-2013
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*GELTAMO-2006: [[#R-MegaCHOP|R-MegaCHOP]] x 3, then [[#R-IFE_2|R-IFE]] x 2
 
−
*ORCHARRD: [[#O-DHAP|O-DHAP]] x 3 versus [[#R-DHAP|R-DHAP]] x 3
 
−
{{#lst:Autologous HSCT|fa5ca4}}
 
−
'''Stem cells reinfused on day 0'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2 {{#subobject:445dc0|Variant=1}}===
 
−
{| class="wikitable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/111/2/537.long Vellenga et al. 2008 (HOVON-44)]
 
−
|2000-2005
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664033/ Gisselbrecht et al. 2010 (CORAL)]
 
−
|2003-2007
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Preceding treatment====
 
−
*HOVON-44: [[#DHAP.2FVIM_88|DHAP/VIM]] versus [[#R-DHAP.2FR-VIM|R-DHAP/R-VIM]]
 
−
*CORAL: [[#R-ICE|R-ICE]] x 3 versus [[#R-DHAP|R-DHAP]] x 3
 
−
{{#lst:Autologous HSCT|c92668}}
 
−
'''Stem cells reinfused on day 0'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Subsequent treatment====
 
−
*CORAL: [[#Rituximab_monotherapy_2|Rituximab]] maintenance versus [[Diffuse_large_B-cell_lymphoma_-_null_regimens#Observation_2|observation]]
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 300/100q12/200/140 {{#subobject:76416d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM198706113162401 Philip et al. 1987]
 
−
|1980-1985
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|}
 
−
{{#lst:Autologous HSCT|76416d}}
 
−
</div></div>
 
−
===References===
 
−
#Philip T, Armitage JO, Spitzer G, Chauvin F, Jagannath S, Cahn JY, Colombat P, Goldstone AH, Gorin NC, Flesh M, Laporte JP, Maraninchi D, Pico J, Bosly A, Anderson C, Schots R, Biron P, Cabanillas F, Dicke K. High-dose therapy and autologous bone marrow transplantation after failure of conventional chemotherapy in adults with intermediate-grade or high-grade non-Hodgkin's lymphoma. N Engl J Med. 1987 Jun 11;316(24):1493-8. [https://doi.org/10.1056/NEJM198706113162401 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/3295541 PubMed]
 
−
#'''HOVON-44:''' Vellenga E, van Putten WL, van 't Veer MB, Zijlstra JM, Fibbe WE, van Oers MH, Verdonck LF, Wijermans PW, van Imhoff GW, Lugtenburg PJ, Huijgens PC. Rituximab improves the treatment results of DHAP-VIM-DHAP and ASCT in relapsed/progressive aggressive CD20+ NHL: a prospective randomized HOVON trial. Blood. 2008 Jan 15;111(2):537-43. [http://www.bloodjournal.org/content/111/2/537.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17971487 PubMed] NCT00012051
 
−
<!--
 
−
Presented at the 45th Annual Meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL, and at the 51st Annual Meeting of the American Society of Hematology, December 5-8, 2009, New Orleans, LA. -->
 
−
#'''CORAL:''' Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Brière J, Moskowitz CH, Schmitz N. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010 Sep 20;28(27):4184-90. Epub 2010 Jul 26. Erratum in: J Clin Oncol. 2012 May 20;30(15):1896. [https://doi.org/10.1200/jco.2010.28.1618 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664033/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20660832 PubMed] NCT00137995
 
−
#'''SHEBA-07-4466-AN-CTIL:''' Shimoni A, Avivi I, Rowe JM, Yeshurun M, Levi I, Or R, Patachenko P, Avigdor A, Zwas T, Nagler A. A randomized study comparing yttrium-90 ibritumomab tiuxetan (Zevalin) and high-dose BEAM chemotherapy versus BEAM alone as the conditioning regimen before autologous stem cell transplantation in patients with aggressive lymphoma. Cancer. 2012 Oct 1;118(19):4706-14. Epub 2012 Jan 17. [https://doi.org/10.1002/cncr.27418 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22252613 PubMed] NCT00491491
 
−
#'''GELTAMO-2006:''' Pardal E, Coronado M, Martín A, Grande C, Marín-Niebla A, Panizo C, Bello JL, Conde E, Hernández MT, Arranz R, Bargay J, González-Barca E, Pérez-Ceballos E, Montes-Moreno S, Caballero MD. Intensification treatment based on early FDG-PET in patients with high-risk diffuse large B-cell lymphoma: a phase II GELTAMO trial. Br J Haematol. 2014 Nov;167(3):327-36. Epub 2014 Jul 28. [https://doi.org/10.1111/bjh.13036 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25066542 PubMed] NCT013611091
 
−
#'''ORCHARRD:''' van Imhoff GW, McMillan A, Matasar MJ, Radford J, Ardeshna KM, Kuliczkowski K, Kim W, Hong X, Goerloev JS, Davies A, Barrigón MD, Ogura M, Leppä S, Fennessy M, Liao Q, van der Holt B, Lisby S, Hagenbeek A. Ofatumumab versus rituximab salvage chemoimmunotherapy in relapsed or refractory diffuse large B-cell lymphoma: the ORCHARRD study. J Clin Oncol. 2017 Feb 10;35(5):544-51. Epub 2016 Dec 28. [https://doi.org/10.1200/JCO.2016.69.0198 link to original article] [https://ascopubs.org/doi/suppl/10.1200/JCO.2016.69.0198/suppl_file/ds_2016.690198.pdf link to data supplement] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28029326 PubMed] NCT01014208
 
−
==BeEAM, then auto HSCT {{#subobject:dee72f|Regimen=1}}==
 
−
BeEAM: '''<u>Be</u>'''ndamustine, '''<u>E</u>'''toposide, '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''elphalan
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:81ff2e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/118/12/3419.long Visani et al. 2011]
 
−
|2008-2010
 
−
| style="background-color:#ffffbe" |Phase 1/2, <20 pts in this subgroup
 
−
|-
 
−
|}
 
−
{{#lst:Autologous HSCT|81ff2e}}
 
−
</div></div>
 
−
===References===
 
−
#Visani G, Malerba L, Stefani PM, Capria S, Galieni P, Gaudio F, Specchia G, Meloni G, Gherlinzoni F, Giardini C, Falcioni S, Cuberli F, Gobbi M, Sarina B, Santoro A, Ferrara F, Rocchi M, Ocio EM, Caballero MD, Isidori A. BeEAM (bendamustine, etoposide, cytarabine, melphalan) before autologous stem cell transplantation is safe and effective for resistant/relapsed lymphoma patients. Blood. 2011 Sep 22;118(12):3419-25. Epub 2011 Aug 3. [http://www.bloodjournal.org/content/118/12/3419.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21816830 PubMed] EudraCT 2008-002736-15
 
−
==CBV, then auto HSCT {{#subobject:935235|Regimen=1}}==
 
−
CBV: '''<u>C</u>'''yclophosphamide, '''<u>B</u>'''iCNU (Carmustine), '''<u>V</u>'''P-16 (Etoposide)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:35a696|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.1998.16.1.48 Stiff et al. 1998]
 
−
|NR in abstract
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
{{#lst:Autologous HSCT|35a696}}
 
−
</div></div>
 
−
===References===
 
−
#Stiff PJ, Dahlberg S, Forman SJ, McCall AR, Horning SJ, Nademanee AP, Blume KG, LeBlanc M, Fisher RI; [[Study_Groups#SWOG|SWOG]]. Autologous bone marrow transplantation for patients with relapsed or refractory diffuse aggressive non-Hodgkin's lymphoma: value of augmented preparative regimens--a Southwest Oncology Group trial. J Clin Oncol. 1998 Jan;16(1):48-55. [https://doi.org/10.1200/jco.1998.16.1.48 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9440722 PubMed]
 
−
==Cyclophosphamide & TBI, then auto HSCT {{#subobject:0a4915|Regimen=1}}==
 
−
Cy/TBI: '''<u>Cy</u>'''clophosphamide & '''<u>T</u>'''otal '''<u>B</u>'''ody '''<u>I</u>'''rradiation
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:a2b2d3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJM198406143102403 Phillips et al. 1984]
 
−
|1977-1982
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
|-
 
−
|}
 
−
{{#lst:Autologous HSCT|a2b2d3}}
 
−
</div></div>
 
−
===References===
 
−
#Phillips GL, Herzig RH, Lazarus HM, Fay JW, Wolff SN, Mill WB, Lin H, Thomas PR, Glasgow GP, Shina DC, Herzig GP. Treatment of resistant malignant lymphoma with cyclophosphamide, total body irradiation, and transplantation of cryopreserved autologous marrow. N Engl J Med. 1984 Jun 14;310(24):1557-61. [https://doi.org/10.1056/NEJM198406143102403 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6374452 PubMed]
 
−
==FEAM, then auto HSCT {{#subobject:0aac6f|Regimen=1}}==
 
−
FEAM: '''<u>F</u>'''otemustine, '''<u>E</u>'''toposide, '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''elphalan
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:74d43c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1038/bmt.2009.318 Musso et al. 2009]
 
−
|2007-2008
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
{{#lst:Autologous HSCT|74d43c}}
 
−
</div></div>
 
−
===References===
 
−
#Musso M, Scalone R, Marcacci G, Lanza F, Di Renzo N, Cascavilla N, Di Bartolomeo P, Crescimanno A, Perrone T, Pinto A. Fotemustine plus etoposide, cytarabine and melphalan (FEAM) as a new conditioning regimen for lymphoma patients undergoing auto-SCT: a multicenter feasibility study. Bone Marrow Transplant. 2010 Jul;45(7):1147-53. Epub 2009 Nov 9. [https://doi.org/10.1038/bmt.2009.318 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19898504 PubMed]
 
−
==FluBuCy, then allo HSCT {{#subobject:84acb0|Regimen=1}}==
 
−
FluBuCy: '''<u>Flu</u>'''darabine, '''<u>Bu</u>'''sulfan, '''<u>Cy</u>'''clophosphamide
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:bfe434|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70161-5 Glass et al. 2014 (DSHNHL R3)]
 
−
|2004-2009
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
{{#lst:Allogeneic HSCT|bfe434}}
 
−
====Immunotherapy====
 
−
*[[Allogeneic stem cells]]
 
−
'''Stem cells transfused on day 0'''
 
−
</div></div>
 
−
===References===
 
−
<!-- # Glass B, rabbits Kamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M Silling G, Wilhelm C, Zeis M, Görlitz A, Pfeiffer S, Hilgers R, Truemper L, Schmitz N. High-dose chemotherapy Followed by allogeneic stem cell transplantation in relapsed and refractory high-risk aggressive non-Hodgkin's lymphoma: Results of a prospective study of the German high-grade non-Hodgkin's lymphoma study group. J Clin Oncol 30, 2012 (suppl; abstr 8004) -->
 
−
#'''DSHNHL R3:''' Glass B, Hasenkamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M, Silling G, Wilhelm C, Zeis M, Görlitz A, Pfeiffer S, Hilgers R, Truemper L, Schmitz N; German High-Grade Lymphoma Study Group. Rituximab after lymphoma-directed conditioning and allogeneic stem-cell transplantation for relapsed and refractory aggressive non-Hodgkin lymphoma (DSHNHL R3): an open-label, randomised, phase 2 trial. Lancet Oncol. 2014 Jun;15(7):757-66. Epub 2014 May 11. [https://doi.org/10.1016/S1470-2045(14)70161-5 link to original article] [http://www.dshnhl.org/app/download/9495510598/Studienprotokoll+DSHNHL+alloFBC+final+vollst.pdf link to original protocol (in German)] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24827808 PubMed] NCT00785330
 
−
==Fludarabine, Busulfan, ATG, Ibritumomab tiuxetan, then allo HSCT {{#subobject:68bee2|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:822e5a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdu503 Bouabdallah et al. 2015 (ZEVALLO)]
 
−
|2008-2010
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
{{#lst:Allogeneic HSCT|822e5a}}
 
−
====Immunotherapy====
 
−
*[[Allogeneic stem cells]]
 
−
'''Stem cells transfused on day 0'''
 
−
</div></div>
 
−
===References===
 
−
#'''ZEVALLO:''' Bouabdallah K, Furst S, Asselineau J, Chevalier P, Tournilhac O, Ceballos P, Vigouroux S, Tabrizi R, Doussau A, Bouabdallah R, Mohty M, Le Gouill S, Blaise D, Milpied N. 90Y-ibritumomab tiuxetan, fludarabine, busulfan and antithymocyte globulin reduced-intensity allogeneic transplant conditioning for patients with advanced and high-risk B-cell lymphomas. Ann Oncol. 2015 Jan;26(1):193-8. Epub 2014 Oct 30. [https://doi.org/10.1093/annonc/mdu503 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25361987 PubMed] NCT00607854
 
−
==LEED, then auto HSCT {{#subobject:bf49e4|Regimen=1}}==
 
−
LEED: '''<u>L</u>'''-PAM (Melphalan), '''<u>E</u>'''ndoxan (Cyclophosphamide), '''<u>E</u>'''toposide, '''<u>D</u>'''examethasone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:a8ec2f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2016.69.0198 van Imhoff et al. 2016 (ORCHARRD)]
 
−
|2010-2013
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase III RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#O-DHAP|O-DHAP]] x 3 versus [[#R-DHAP|R-DHAP]] x 3
 
−
{{#lst:Autologous HSCT conditioning regimens|47e3df}}
 
−
'''Stem cells reinfused on day 0'''
 
−
</div></div>
 
−
===References===
 
−
#'''ORCHARRD:''' van Imhoff GW, McMillan A, Matasar MJ, Radford J, Ardeshna KM, Kuliczkowski K, Kim W, Hong X, Goerloev JS, Davies A, Barrigón MD, Ogura M, Leppä S, Fennessy M, Liao Q, van der Holt B, Lisby S, Hagenbeek A. Ofatumumab versus rituximab salvage chemoimmunotherapy in relapsed or refractory diffuse large B-cell lymphoma: the ORCHARRD study. J Clin Oncol. 2017 Feb 10;35(5):544-51. Epub 2016 Dec 28. [https://doi.org/10.1200/JCO.2016.69.0198 link to original article] [https://ascopubs.org/doi/suppl/10.1200/JCO.2016.69.0198/suppl_file/ds_2016.690198.pdf link to data supplement] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28029326 PubMed] NCT01014208
 
−
==R-BEAM, then auto HSCT {{#subobject:8b88db|Regimen=1}}==
 
−
R-BEAM: '''<u>R</u>'''ituximab, '''<u>B</u>'''iCNU (Carmustine), '''<u>E</u>'''toposide, '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''elphalan
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 750/300/800/800/140 {{#subobject:9131e1|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2012.45.9453 Vose et al. 2013 (BMT CTN 0401)]
 
−
|2006-2009
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#B-BEAM_99|B-BEAM]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS24
 
−
|-
 
−
|}
 
−
''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
 
−
{{#lst:Autologous HSCT|9131e1}}
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 750/300/1600/3200/140 {{#subobject:77f5a0|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.13234 Kirschey et al. 2014 (Mz-135)]
 
−
|2002-2006
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''A minimum number of 2 × 10<sup>6</sup>/kg bw CD34-positive cells were required to proceed.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Preceding treatment====
 
−
*[[#R-DexaBEAM|R-DexaBEAM]] x 2
 
−
{{#lst:Autologous HSCT conditioning regimens|77f5a0}}
 
−
</div></div>
 
−
===References===
 
−
#'''BMT CTN 0401:''' Vose JM, Carter S, Burns LJ, Ayala E, Press OW, Moskowitz CH, Stadtmauer EA, Mineshi S, Ambinder R, Fenske T, Horowitz M, Fisher R, Tomblyn M. Phase III randomized study of rituximab/carmustine, etoposide, cytarabine, and melphalan (BEAM) compared with iodine-131 tositumomab/BEAM with autologous hematopoietic cell transplantation for relapsed diffuse large B-cell lymphoma: results from the BMT CTN 0401 trial. J Clin Oncol. 2013 May 1;31(13):1662-8. Epub 2013 Mar 11. [https://doi.org/10.1200/JCO.2012.45.9453 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3635682/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23478060 PubMed] NCT00329030
 
−
#'''Mz-135:''' Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. [https://doi.org/10.1111/bjh.13234 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25546611 PubMed] NCT02099292
 
−
==R-TBI/Cy, then auto HSCT {{#subobject:38a16a|Regimen=1}}==
 
−
R-TBI/Cy: '''<u>R</u>'''ituximab, '''<u>T</u>'''otal, '''<u>B</u>'''ody, '''<u>I</u>'''rradiation, '''<u>Cy</u>'''clophosphamide
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:1b28ce|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.13234 Kirschey et al. 2014 (Mz-135)]
 
−
|2002-2006
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Preceding treatment====
 
−
*[[#R-DexaBEAM|R-DexaBEAM]] x 2
 
−
{{#lst:Autologous HSCT conditioning regimens|785614}}
 
−
'''Stem cells reinfused on day 0'''
 
−
</div></div>
 
−
===References===
 
−
#'''Mz-135:''' Kirschey S, Flohr T, Wolf HH, Frickhofen N, Gramatzki M, Link H, Basara N, Peter N, Meyer RG, Schmitz N, Weidmann E, Banat A, Schulz A, Kolbe K, Derigs G, Theobald M, Hess G. Rituximab combined with DexaBEAM followed by high dose therapy as salvage therapy in patients with relapsed or refractory B-cell lymphoma: mature results of a phase II multicentre study. Br J Haematol. 2015 Mar;168(6):824-34. Epub 2014 Dec 28. [https://doi.org/10.1111/bjh.13234 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25546611 PubMed] NCT02099292
 
−
==Z-BEAM, then auto HSCT {{#subobject:a6ae5d|Regimen=1}}==
 
−
Z-BEAM: '''<u>Z</u>'''evalin (Ibritumomab tiuxetan), '''<u>B</u>'''iCNU (Carmustine), '''<u>E</u>'''toposide, '''<u>A</u>'''ra-C (Cytarabine), '''<u>M</u>'''elphalan
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:df0b80|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.exphem.org/article/S0301-472X(07)00050-1 Shimoni et al. 2007]
 
−
|2004-2006
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1002/cncr.27418 Shimoni et al. 2012 (SHEBA-07-4466-AN-CTIL)]
 
−
|NR
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 
−
|[[#BEAM.2C_then_auto_HSCT|BEAM]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943314/ Briones et al. 2013 (GELTAMO Z-BEAM LDCGB)]
 
−
|2008-2010
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|}
 
−
''Patients in SHEBA-07-4466-AN-CTIL had primary induction failure or were chemosensitive to salvage therapy. Patients in GELTAMO Z-BEAM LDCGB had primary induction failure or were refractory to salvage therapy.''
 
−
{{#lst:Autologous HSCT|9aeafe}}
 
−
</div></div>
 
−
===References===
 
−
#Shimoni A, Zwas ST, Oksman Y, Hardan I, Shem-Tov N, Yerushalmi R, Avigdor A, Ben-Bassat I, Nagler A. Yttrium-90-ibritumomab tiuxetan (Zevalin) combined with high-dose BEAM chemotherapy and autologous stem cell transplantation for chemo-refractory aggressive non-Hodgkin's lymphoma. Exp Hematol. 2007 Apr;35(4):534-40. [http://www.exphem.org/article/S0301-472X(07)00050-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17379063 PubMed]
 
−
#'''SHEBA-07-4466-AN-CTIL:''' Shimoni A, Avivi I, Rowe JM, Yeshurun M, Levi I, Or R, Patachenko P, Avigdor A, Zwas T, Nagler A. A randomized study comparing yttrium-90 ibritumomab tiuxetan (Zevalin) and high-dose BEAM chemotherapy versus BEAM alone as the conditioning regimen before autologous stem cell transplantation in patients with aggressive lymphoma. Cancer. 2012 Oct 1;118(19):4706-14. Epub 2012 Jan 17. [https://doi.org/10.1002/cncr.27418 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22252613 PubMed] NCT00491491
 
−
#'''GELTAMO Z-BEAM LDCGB:''' Briones J, Novelli S, García-Marco JA, Tomás JF, Bernal T, Grande C, Canales MA, Torres A, Moraleda JM, Panizo C, Jarque I, Palmero F, Hernsández M, González-Barca E, López D, Caballero D. Autologous stem cell transplantation after conditioning with Yttrium-90 ibritumomab tiuxetan plus beam in refractory non-Hodgkin diffuse large B-cell lymphoma: results of a prospective, multicenter, phase II clinical trial. Haematologica. 2014 Mar;99(3):505-10. Epub 2013 Oct 25. [http://www.haematologica.org/content/99/3/505.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943314/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24162789 PubMed] EudraCT 2007-003198-22
 
−
=Maintenance after salvage therapy=
 
−
==Lenalidomide monotherapy {{#subobject:e4284f|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 25 mg 21/28, indefinite {{#subobject:ac6517|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/S2352-3026(17)30016-9 Ferreri et al. 2017]
 
−
|2009-2015
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Preceding treatment====
 
−
*[[Regimen_classes#Rituximab-containing_regimen|Rituximab-containing salvage chemotherapy]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 25 mg 21/28 for 12 months {{#subobject:baf27c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4283736/ Feldman et al. 2014 (RV-DLBCL-PI-0463)]
 
−
|2010-2012
 
−
| style="background-color:#ffffbe" |Phase 1/2, <20 pts
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#BEAM.2C_then_auto_HSCT|BEAM with autologous hematopoietic stem cell transplant (details not described)]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
 
−
'''28-day cycle for up to 13 cycles (1 year)'''
 
−
</div></div>
 
−
===References===
 
−
#'''RV-DLBCL-PI-0463:''' Feldman T, Mato AR, Chow KF, Protomastro EA, Yannotti KM, Bhattacharyya P, Yang X, Donato ML, Rowley SD, Carini C, Valentinetti M, Smith J, Gadaleta G, Bejot C, Stives S, Timberg M, Kdiry S, Pecora AL, Beaven AW, Goy A. Addition of lenalidomide to rituximab, ifosfamide, carboplatin, etoposide (RICER) in first-relapse/primary refractory diffuse large B-cell lymphoma. Br J Haematol. 2014 Jul;166(1):77-83. Epub 2014 Mar 25. [https://doi.org/10.1111/bjh.12846 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4283736/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24661044 PubMed] NCT01241734
 
−
#Ferreri AJ, Sassone M, Zaja F, Re A, Spina M, di Rocco A, Fabbri A, Stelitano C, Frezzato M, Rusconi C, Zambello R, Couto S, Ren Y, Arcari A, Bertoldero G, Nonis A, Scarfò L, Calimeri T, Cecchetti C, Chiozzotto M, Govi S, Ponzoni M. Lenalidomide maintenance in patients with relapsed diffuse large B-cell lymphoma who are not eligible for autologous stem cell transplantation: an open label, single-arm, multicentre phase 2 trial. Lancet Haematol. 2017 Mar;4(3):e137-e146. Epub 2017 Feb 17. [https://doi.org/10.1016/S2352-3026(17)30016-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28219694 PubMed] NCT00799513
 
−
==Rituximab monotherapy {{#subobject:4a4553|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:7bef48|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664033/ Gisselbrecht et al. 2010 (CORAL)]
 
−
|2003-2007
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Diffuse_large_B-cell_lymphoma_-_null_regimens#Observation_2|Observation]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS<sup>1</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2012 update.''<br>
 
−
''Note: Treatment begins on day +28.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#BEAM.2C_then_auto_HSCT|BEAM with autologous hematopoietic stem cell transplant]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
'''8-week cycle for 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- Presented at the 45th Annual Meeting of the American Society of Clinical Oncology, June 4-6, 2011, Chicago, IL. -->
 
−
#'''CORAL:''' Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Brière J, Moskowitz CH, Schmitz N. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010 Sep 20;28(27):4184-90. Epub 2010 Jul 26. Erratum in: J Clin Oncol. 2012 May 20;30(15):1896. [https://doi.org/10.1200/jco.2010.28.1618 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3664033/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20660832 PubMed] NCT00137995
 
−
##'''Update:''' Gisselbrecht C, Schmitz N, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Milpied NJ, Radford J, Ketterer N, Shpilberg O, Dührsen U, Hagberg H, Ma DD, Viardot A, Lowenthal R, Brière J, Salles G, Moskowitz CH, Glass B. Rituximab maintenance therapy after autologous stem-cell transplantation in patients with relapsed CD20(+) diffuse large B-cell lymphoma: final analysis of the collaborative trial in relapsed aggressive lymphoma. J Clin Oncol. 2012 Dec 20;30(36):4462-9. Epub 2012 Oct 22. [https://doi.org/10.1200/jco.2012.41.9416 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646314/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23091101 PubMed]
 
−
=Relapsed or refractory, further lines of therapy=
 
−
''Note: these are regimens that are generally given with non-curative intent. However, some of these regimens, such as CAR-T therapy, can function as a bridge to consolidation with one of the salvage consolidation regimens, above.''
 
−
==Axicabtagene ciloleucel monotherapy {{#subobject:78231d|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:e3e516|Variant=1}}===
 
−
{| class="wikitable" style="color:white; background-color:#404040"
 
−
|<small>'''FDA-recommended dose'''</small>
 
−
|-
 
−
|}
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363293/ Locke et al. 2017 (ZUMA-1)]
 
−
|2015-2016
 
−
| style="background-color:#91cf61" |Phase 1/2 (RT)
 
−
|ORR: 83%; CR: 59%
 
−
Median OS: not reached
 
−
Median PFS: 6 months
 
−
Median duration of response: 11 months
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy, lymphodepletion====
 
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once per day on days -5 to -3 prior to [[Axicabtagene ciloleucel (Yescarta)|Axicabtagene ciloleucel]] infusion
 
−
*[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days -5 to -3 prior to [[Axicabtagene ciloleucel (Yescarta)|Axicabtagene ciloleucel]] infusion
 
−
====Immunotherapy====
 
−
*[[Axicabtagene ciloleucel (Yescarta)]] target dose of 2 × 10<sup>6</sup> CAR T cells/kg IV once on day 0
 
−
====Supportive therapy====
 
−
*[[Acetaminophen (Tylenol)]] 650 mg PO once on day 0, approximately 60 minutes prior to [[Axicabtagene ciloleucel (Yescarta)]]
 
−
*[[Diphenhydramine (Benadryl)]] 12.5 mg IV or PO once on day 0, approximately 60 minutes prior to [[Axicabtagene ciloleucel (Yescarta)]]
 
−
 
−
'''One course; patients with initial response and disease progression at least 3 months later could be retreated'''
 
−
</div></div>
 
−
===References===
 
−
#'''ZUMA-1:''' Locke FL, Neelapu SS, Bartlett NL, Siddiqi T, Chavez JC, Hosing CM, Ghobadi A, Budde LE, Bot A, Rossi JM, Jiang Y, Xue AX, Elias M, Aycock J, Wiezorek J, Go WY. Phase 1 results of ZUMA-1: A multicenter study of KTE-C19 anti-CD19 CAR T cell therapy in refractory aggressive lymphoma. Mol Ther. 2017 Jan 4;25(1):285-295. Epub 2017 Jan 4. [https://doi.org/10.1016/j.ymthe.2016.10.020 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363293/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28129122 PubMed] NCT02348216
 
−
##'''Update:''' Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, Stiff PJ, Friedberg JW, Flinn IW, Goy A, Hill BT, Smith MR, Deol A, Farooq U, McSweeney P, Munoz J, Avivi I, Castro JE, Westin JR, Chavez JC, Ghobadi A, Komanduri KV, Levy R, Jacobsen ED, Witzig TE, Reagan P, Bot A, Rossi J, Navale L, Jiang Y, Aycock J, Elias M, Chang D, Wiezorek J, Go WY. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017 Dec 28;377(26):2531-2544. Epub 2017 Dec 10. [https://doi.org/10.1056/NEJMoa1707447 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882485/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29226797 PubMed]
 
−
##'''Update:''' Locke FL, Ghobadi A, Jacobson CA, Miklos DB, Lekakis LJ, Oluwole OO, Lin Y, Braunschweig I, Hill BT, Timmerman JM, Deol A, Reagan PM, Stiff P, Flinn IW, Farooq U, Goy A, McSweeney PA, Munoz J, Siddiqi T, Chavez JC, Herrera AF, Bartlett NL, Wiezorek JS, Navale L, Xue A, Jiang Y, Bot A, Rossi JM, Kim JJ, Go WY, Neelapu SS. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 2019 Jan;20(1):31-42. Epub 2018 Dec 2. [https://doi.org/10.1016/S1470-2045(18)30864-7 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733402/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30518502 PubMed]
 
−
==Bendamustine monotherapy {{#subobject:78231d|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:e3e516|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdf189 Weidmann et al. 2002]
 
−
|NR
 
−
| style="background-color:#ffffbe" |Phase 2, <20 pts
 
−
|ORR: 44%
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Bendamustine]] 120 mg/m<sup>2</sup> IV once per day on days 1 & 2
 
−
'''21-day cycle for up to 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#Weidmann E, Kim SZ, Rost A, Schuppert H, Seipelt G, Hoelzer D, Mitrou PS. Bendamustine is effective in relapsed or refractory aggressive non-Hodgkin's lymphoma. Ann Oncol. 2002 Aug;13(8):1285-9. [https://doi.org/10.1093/annonc/mdf189 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12181253 PubMed]
 
−
==Blinatumomab monotherapy {{#subobject:4c5004|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:94f800|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4797019/ Viardot et al. 2016 (MT103-208)]
 
−
|2012-2014
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Two dosing schemas were evaluated; this is the preferred dosing regimen, per the authors.''
 
−
====Immunotherapy====
 
−
*[[Blinatumomab (Blincyto)]] as follows:
 
−
**Week 1: 9 mcg/day IV continuous infusion
 
−
**Week 2: 28 mcg/day IV continuous infusion
 
−
**Weeks 3 to 8: 112 mcg/day IV continuous infusion
 
−
====Supportive therapy====
 
−
*[[Dexamethasone (Decadron)]] 20 mg PO 6 to 12 hours before infusion start and dose increases, 20 mg PO 1 hour before infusion start and dose increases, and 8 mg PO three times per day for 2 days following infusion start and dose increases
 
−
**Patients with neurologic symptoms or cytokine release syndrome received 8 mg IV or PO every 8 hours for up to 3 days, with a subsequent taper over 4 days
 
−
'''8-week course'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Responders could receive a 4-week consolidation cycle after a 4-week treatment-free period. Patients relapsing within 2 years of treatment could receive another 8-week course.
 
−
</div></div>
 
−
===References===
 
−
<!--Presented in abstract form at the 55th annual meeting (New Orleans, LA, December 2013) and the 56th annual meeting (San Francisco, CA, December 2014) of the American Society of Hematology; the 2015 annual meeting of the American Society of Clinical Oncology (Chicago, IL, June 2015); and the 13th International Conference on Malignant Lymphoma (Lugano, Switzerland, June 2015). -->
 
−
#'''MT103-208:''' Viardot A, Goebeler ME, Hess G, Neumann S, Pfreundschuh M, Adrian N, Zettl F, Libicher M, Sayehli C, Stieglmaier J, Zhang A, Nagorsen D, Bargou RC. Phase 2 study of the bispecific T-cell engager (BiTE) antibody blinatumomab in relapsed/refractory diffuse large B-cell lymphoma. Blood. 2016 Mar 17;127(11):1410-6. Epub 2016 Jan 11. [http://www.bloodjournal.org/content/127/11/1410.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4797019/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26755709 PubMed] NCT01741792
 
−
==Bendamustine & Rituximab (BR) {{#subobject:1bb486|Regimen=1}}==
 
−
BR: '''<u>B</u>'''endamustine & '''<u>R</u>'''ituximab
 
−
R-B: '''<u>R</u>'''ituximab & '''<u>B</u>'''endamustine
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 6 cycles {{#subobject:87e6f7|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3918114/ Vacirca et al. 2013 (PI-08904)]
 
−
|2008-2011
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2012.46.5203 Ohmachi et al. 2013 (SymBio 2010001)]
 
−
|2010-2011
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Note: Bendamustine was given on days 2 & 3 in SymBio 2010001 and on days 1 & 2 in PI-08904.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Bendamustine]] 120 mg/m<sup>2</sup> IV once per day on days 1 & 2 OR on days 2 & 3
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Supportive therapy====
 
−
*Recommended PCP prophylaxis: [[Trimethoprim-Sulfamethoxazole (Bactrim DS)]]
 
−
*Recommended VZV prophylaxis: [[Acyclovir (Zovirax)]]
 
−
'''21-day cycle for up to 6 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, indefinite {{#subobject:87ea7c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6200343/ Dang et al. 2017 (B1931008)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Diffuse_large_B-cell_lymphoma_-_historical#R-INO|R-INO]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Bendamustine]] 120 mg/m<sup>2</sup> IV once per day on days 1 & 2
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- Presented at the 48th Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2012, Chicago, IL. -->
 
−
#'''SymBio 2010001:''' Ohmachi K, Niitsu N, Uchida T, Kim SJ, Ando K, Takahashi N, Takahashi N, Uike N, Eom HS, Chae YS, Terauchi T, Tateishi U, Tatsumi M, Kim WS, Tobinai K, Suh C, Ogura M. Multicenter phase II study of bendamustine plus rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol. 2013 Jun 10;31(17):2103-9. Epub 2013 May 6. [https://doi.org/10.1200/jco.2012.46.5203 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23650408 PubMed] NCT01118845
 
−
#'''PI-08904:''' Vacirca JL, Acs PI, Tabbara IA, Rosen PJ, Lee P, Lynam E. Bendamustine combined with rituximab for patients with relapsed or refractory diffuse large B cell lymphoma. Ann Hematol. 2014 Mar;93(3):403-9. Epub 2013 Aug 17. [http://link.springer.com/article/10.1007/s00277-013-1879-x link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3918114/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23955074 PubMed] NCT00831597
 
−
#'''B1931008:''' Dang NH, Ogura M, Castaigne S, Fayad LE, Jerkeman M, Radford J, Pezzutto A, Bondarenko I, Stewart DA, Shnaidman M, Sullivan S, Vandendries E, Tobinai K, Ramchandren R, Hamlin PA, Giné E, Ando K. Randomized, phase 3 trial of inotuzumab ozogamicin plus rituximab versus chemotherapy plus rituximab for relapsed/refractory aggressive B-cell non-Hodgkin lymphoma. Br J Haematol. 2018 Aug;182(4):583-586. Epub 2017 Jul 5. [https://doi.org/full/10.1111/bjh.14820 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6200343/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28677896 PubMed] NCT01232556
 
−
#'''GO29365:''' Sehn LH, Herrera AF, Flowers CR, Kamdar MK, McMillan A, Hertzberg M, Assouline S, Kim TM, Kim WS, Ozcan M, Hirata J, Penuel E, Paulson JN, Cheng J, Ku G, Matasar MJ. Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma. J Clin Oncol. 2020 Jan 10; 38(2):155-165. Epub 2019 Nov 6. [https://doi.org/10.1200/JCO.19.00172 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31693429 link to pubmed] NCT02257567
 
−
##'''Update:''' Sehn LH, Hertzberg M, Opat S, Herrera AF, Assouline S, Flowers CR, Kim TM, McMillan A, Ozcan M, Safar V, Salles G, Ku G, Hirata J, Chang YM, Musick L, Matasar MJ. Polatuzumab vedotin plus bendamustine and rituximab in relapsed/refractory DLBCL: survival update and new extension cohort data. Blood Adv. 2022 Jan 25;6(2):533-543. [https://doi.org/10.1182/bloodadvances.2021005794 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8791582/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34749395/ PubMed]
 
−
==Bendamustine & Rituximab (BR) & Polatuzumab vedotin {{#subobject:1cc486|Regimen=1}}==
 
−
BR & Polatuzumab vedotin: '''<u>B</u>'''endamustine, '''<u>R</u>'''ituximab, Polatuzumab vedotin
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:26c6f7|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.19.00172 Sehn et al. 2019 (GO29365)]
 
−
|2014-2016
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-RT-esc)
 
−
|[[#Bendamustine_.26_Rituximab_.28BR.29_2|BR]]
 
−
| style="background-color:#91cf60" |Seems to have superior ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Bendamustine]] as follows:
 
−
**Cycle 1: 90 mg/m<sup>2</sup> IV once per day on days 2 & 3
 
−
**Cycles 2 to 6: 90 mg/m<sup>2</sup> IV once per day on days 1 & 2
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Antibody-drug conjugate therapy====
 
−
*[[Polatuzumab vedotin (Polivy)]] as follows:
 
−
**Cycle 1: 1.8 mg/kg IV over 90 minutes once on day 2
 
−
**Cycles 2 to 6: 1.8 mg/kg IV over 90 minutes once on day 1
 
−
</div></div>
 
−
===References===
 
−
#'''GO29365:''' Sehn LH, Herrera AF, Flowers CR, Kamdar MK, McMillan A, Hertzberg M, Assouline S, Kim TM, Kim WS, Ozcan M, Hirata J, Penuel E, Paulson JN, Cheng J, Ku G, Matasar MJ. Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma. J Clin Oncol. 2020 Jan 10; 38(2):155-165. Epub 2019 Nov 6. [https://doi.org/10.1200/JCO.19.00172 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31693429 link to pubmed] NCT02257567
 
−
##'''Update:''' Sehn LH, Hertzberg M, Opat S, Herrera AF, Assouline S, Flowers CR, Kim TM, McMillan A, Ozcan M, Safar V, Salles G, Ku G, Hirata J, Chang YM, Musick L, Matasar MJ. Polatuzumab vedotin plus bendamustine and rituximab in relapsed/refractory DLBCL: survival update and new extension cohort data. Blood Adv. 2022 Jan 25;6(2):533-543. [https://doi.org/10.1182/bloodadvances.2021005794 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8791582/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34749395/ PubMed]
 
−
==Brentuximab vedotin monotherapy {{#subobject:d4dff2|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:965d6b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/125/9/1394 Jacobsen et al. 2015 (SGN35-012)]
 
−
|2011-2013
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Jacobsen et al. 2015 treated patients with CD30+ non-Hodgkin lymphoma, as determined by IHC; the 2016 update describes a subgroup with undetectable CD30.''
 
−
====Antibody-drug conjugate therapy====
 
−
*[[Brentuximab vedotin (Adcetris)]] 1.8 mg/kg IV over 30 minutes once on day 1
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- '''Abstract:''' Nancy L. Bartlett, MD, Jeff P. Sharman, MD, Yasuhiro Oki, MD, Ranjana H. Advani, MD, Celeste M. Bello, MD, Jane N. Winter, MD, Yin Yang, MS, Dana A. Kennedy, PharmD and Eric D. Jacobsen, MD. A Phase 2 Study Of Brentuximab Vedotin In Patients With Relapsed Or Refractory CD30-Positive Non-Hodgkin Lymphomas: Interim Results In Patients With DLBCL and Other B-Cell Lymphomas. ASH Abstract 848. [https://ash.confex.com/ash/2013/webprogram/Paper59695.html link to abstract] -->
 
−
#'''SGN35-012:''' Jacobsen ED, Sharman JP, Oki Y, Advani RH, Winter JN, Bello CM, Spitzer G, Palanca-Wessels MC, Kennedy DA, Levine P, Yang J, Bartlett NL. Brentuximab vedotin demonstrates objective responses in a phase 2 study of relapsed/refractory DLBCL with variable CD30 expression. Blood. 2015 Feb 26;125(9):1394-402. Epub 2015 Jan 8. [http://www.bloodjournal.org/content/125/9/1394 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25573987 PubMed] NCT01421667
 
−
<!-- # '''Abstract:''' Nancy L. Bartlett, MD, Mitchell R. Smith, MD, Ranjana Advani, MD, Tatyana Feldman, MD, Kerry J. Savage, MD MSc, Maria Corinna Palanca-Wessels, MD, PhD and Tanya Siddiqi, MD. Brentuximab Vedotin Monotherapy in DLBCL Patients with Undetectable CD30: Preliminary Results from a Phase 2 Study. ASH Annual Meeting 2014 Abstract 629 [https://ash.confex.com/ash/2014/webprogram/Paper67042.html link to abstract] -->
 
−
##'''Update:''' Bartlett NL, Smith MR, Siddiqi T, Advani RH, O'Connor OA, Sharman JP, Feldman T, Savage KJ, Shustov AR, Diefenbach CS, Oki Y, Palanca-Wessels MC, Uttarwar M, Li M, Yang J, Jacobsen ED. Brentuximab vedotin activity in diffuse large B-cell lymphoma with CD30 undetectable by visual assessment of conventional immunohistochemistry. Leuk Lymphoma. 2017 Jul;58(7):1607-1616. Epub 2016 Nov 20. [https://doi.org/10.1080/10428194.2016.1256481 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27868471 PubMed]
 
−
==Etoposide monotherapy {{#subobject:1ed00b|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, IV (3 days/cycle) {{#subobject:7a80fc|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://clincancerres.aacrjournals.org/content/23/15/4127.long Czuczman et al. 2017 (DLC-001)]
 
−
|2009-2013
 
−
| style="background-color:#1a9851" |Phase 2/3 (C)
 
−
|[[#Lenalidomide_monotherapy_3|Lenalidomide]]
 
−
| style="background-color:#fee08b" |Might have inferior ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
 
−
'''28-day cycle for up to 6 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, IV (5 days/cycle) {{#subobject:1bece4|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(12)70212-7 Pettengell et al. 2012 (PIX301)]
 
−
|2004-2008
 
−
| style="background-color:#91cf61" |Phase 3, <20 pts in this arm (C)
 
−
|[[#Pixantrone_monotherapy|Pixantrone]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior CR/CRu rate
 
−
|-
 
−
|[http://clincancerres.aacrjournals.org/content/23/15/4127.long Czuczman et al. 2017 (DLC-001)]
 
−
|2009-2013
 
−
| style="background-color:#1a9851" |Phase 2/3 (C)
 
−
|[[#Lenalidomide_monotherapy_3|Lenalidomide]]
 
−
| style="background-color:#fee08b" |Might have inferior ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 5
 
−
'''28-day cycle for up to 6 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, PO (10 days/cycle) {{#subobject:c6531a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://clincancerres.aacrjournals.org/content/23/15/4127.long Czuczman et al. 2017 (DLC-001)]
 
−
|2009-2013
 
−
| style="background-color:#1a9851" |Phase 2/3 (C)
 
−
|[[#Lenalidomide_monotherapy_3|Lenalidomide]]
 
−
| style="background-color:#fee08b" |Might have inferior ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup> PO once per day on days 1 to 10
 
−
'''28-day cycle for up to 6 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #4, PO (14 days/cycle) {{#subobject:f3bee1|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://clincancerres.aacrjournals.org/content/23/15/4127.long Czuczman et al. 2017 (DLC-001)]
 
−
|2009-2013
 
−
| style="background-color:#1a9851" |Phase 2/3 (C)
 
−
|[[#Lenalidomide_monotherapy_3|Lenalidomide]]
 
−
| style="background-color:#fee08b" |Might have inferior ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup> PO once per day on days 1 to 14
 
−
'''28-day cycle for up to 6 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #5, PO (21 days/cycle) {{#subobject:929913|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://link.springer.com/chapter/10.1007/978-3-642-78350-0_29 Hainsworth et al. 1992]
 
−
|1988-1989
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(12)70212-7 Pettengell et al. 2012 (PIX301)]
 
−
|2004-2008
 
−
| style="background-color:#91cf61" |Phase 3, <20 pts in this arm (C)
 
−
|[[#Pixantrone_monotherapy|Pixantrone]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior CR/CRu rate
 
−
|-
 
−
|[http://clincancerres.aacrjournals.org/content/23/15/4127.long Czuczman et al. 2017 (DLC-001)]
 
−
|2009-2013
 
−
| style="background-color:#1a9851" |Phase 2/3 (C)
 
−
|[[#Lenalidomide_monotherapy_3|Lenalidomide]]
 
−
| style="background-color:#fee08b" |Might have inferior ORR
 
−
|-
 
−
|}
 
−
''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup> PO once per day on days 1 to 21
 
−
'''28-day cycle for up to 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#Hainsworth JD, Johnson DH, Greco FA. Chronic etoposide schedules in the treatment of non-Hodgkin's lymphoma. Semin Oncol. 1992 Dec;19(6 Suppl 14):13-8. [https://link.springer.com/chapter/10.1007/978-3-642-78350-0_29 link to original article] [https://pubmed.ncbi.nlm.nih.gov/1488651 PubMed]
 
−
#'''PIX301:''' Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. [https://doi.org/10.1016/S1470-2045(12)70212-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22652183 PubMed] NCT00088530
 
−
#'''DLC-001:''' Czuczman MS, Trněný M, Davies A, Rule S, Linton KM, Wagner-Johnston N, Gascoyne RD, Slack GW, Brousset P, Eberhard DA, Hernandez-Ilizaliturri FJ, Salles G, Witzig TE, Zinzani PL, Wright GW, Staudt LM, Yang Y, Williams PM, Lih CJ, Russo J, Thakurta A, Hagner P, Fustier P, Song D, Lewis ID. A phase 2/3 multicenter, randomized, open-label study to compare the efficacy and safety of lenalidomide versus investigator's choice in patients with relapsed or refractory diffuse large B-cell lymphoma. Clin Cancer Res. 2017 Aug 1;23(15):4127-4137. Epub 2017 Apr 5. [http://clincancerres.aacrjournals.org/content/23/15/4127.long link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28381416 PubMed] EudraCT 2009-013483-38
 
−
==Everolimus monotherapy {{#subobject:fb3cbd|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:9aafa|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3049870/ Witzig et al. 2011]
 
−
|2005-2008
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Everolimus (Afinitor)]] 10 mg PO once per day on an empty stomach
 
−
====Supportive therapy====
 
−
*"Patients could receive white blood cell growth factors, if neutropenia developed at physician's discretion. Erythropoietin treatment for anemia was permitted per standard guidelines."
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#Witzig TE, Reeder CB, LaPlant BR, Gupta M, Johnston PB, Micallef IN, Porrata LF, Ansell SM, Colgan JP, Jacobsen ED, Ghobrial IM, Habermann TM. A phase II trial of the oral mTOR inhibitor everolimus in relapsed aggressive lymphoma. Leukemia. 2011 Feb;25(2):341-7. Epub 2010 Dec 7. [https://doi.org/10.1038/leu.2010.226 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3049870/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21135857 PubMed]
 
−
==Everolimus & Rituximab {{#subobject:bae86f|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:9621eb|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659994/ Barnes et al. 2013 (MGH 09-002)]
 
−
|2009-2010
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Everolimus (Afinitor)]] as follows:
 
−
**Cycle 1: 5 mg PO once per day on days 1 to 14, then 10 mg PO once per day on days 15 to 28
 
−
**Cycles 2 to 6: 10 mg PO once per day
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
**Cycles 2 to 6: 375 mg/m<sup>2</sup> IV once on day 1
 
−
'''28-day cycle for 6 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Responders had the option of continuing everolimus alone for another 6 months
 
−
</div></div>
 
−
===References===
 
−
#'''MGH 09-002:''' Barnes JA, Jacobsen E, Feng Y, Freedman A, Hochberg EP, LaCasce AS, Armand P, Joyce R, Sohani AR, Rodig SJ, Neuberg D, Fisher DC, Abramson JS. Everolimus in combination with rituximab induces complete responses in heavily pretreated diffuse large B-cell lymphoma. Haematologica. 2013 Apr;98(4):615-9. Epub 2012 Nov 9. [http://www.haematologica.org/content/98/4/615.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659994/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23144193 PubMed] NCT00869999
 
−
==Gemcitabine monotherapy {{#subobject:df3421|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, bi-weekly {{#subobject:5776e8|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://clincancerres.aacrjournals.org/content/23/15/4127.long Czuczman et al. 2017 (DLC-001)]
 
−
|2009-2013
 
−
| style="background-color:#1a9851" |Phase 2/3 (C)
 
−
|[[#Lenalidomide_monotherapy_3|Lenalidomide]]
 
−
| style="background-color:#fee08b" |Might have inferior ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 15
 
−
'''28-day cycle for up to 6 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 3 out of 4 weeks x 6 {{#subobject:853906|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://clincancerres.aacrjournals.org/content/23/15/4127.long Czuczman et al. 2017 (DLC-001)]
 
−
|2009-2013
 
−
| style="background-color:#1a9851" |Phase 2/3 (C)
 
−
|[[#Lenalidomide_monotherapy_3|Lenalidomide]]
 
−
| style="background-color:#fee08b" |Might have inferior ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Gemcitabine (Gemzar)]] 1250 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
'''28-day cycle for up to 6 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, indefinite 3 out of 4 weeks {{#subobject:4d3a21|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.1999.17.12.3786 Fosså et al. 1999]
 
−
|1995-1997
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(12)70212-7 Pettengell et al. 2012 (PIX301)]
 
−
|2004-2008
 
−
| style="background-color:#91cf61" |Phase 3, <20 pts in this arm (C)
 
−
|[[#Pixantrone_monotherapy|Pixantrone]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior CR/CRu rate
 
−
|-
 
−
|}
 
−
''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Gemcitabine (Gemzar)]] as follows:
 
−
**Cycle 1: 1250 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15
 
−
**Fosså et al. 1999, subsequent cycles (if no hematologic or nonhematologic toxicities): Optional increase to 1500 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15
 
−
'''28-day cycle for up to 6 cycles (PIX301) or indefinitely (Fosså et al. 1999)'''
 
−
</div></div>
 
−
===References===
 
−
#Fosså A, Santoro A, Hiddemann W, Truemper L, Niederle N, Buksmaui S, Bonadonna G, Seeber S, Nowrousian MR. Gemcitabine as a single agent in the treatment of relapsed or refractory aggressive non-Hodgkin's lymphoma. J Clin Oncol. 1999 Dec;17(12):3786-92. [https://doi.org/10.1200/jco.1999.17.12.3786 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10577850 PubMed]
 
−
#'''PIX301:''' Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. [https://doi.org/10.1016/S1470-2045(12)70212-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22652183 PubMed] NCT00088530
 
−
#'''DLC-001:''' Czuczman MS, Trněný M, Davies A, Rule S, Linton KM, Wagner-Johnston N, Gascoyne RD, Slack GW, Brousset P, Eberhard DA, Hernandez-Ilizaliturri FJ, Salles G, Witzig TE, Zinzani PL, Wright GW, Staudt LM, Yang Y, Williams PM, Lih CJ, Russo J, Thakurta A, Hagner P, Fustier P, Song D, Lewis ID. A phase 2/3 multicenter, randomized, open-label study to compare the efficacy and safety of lenalidomide versus investigator's choice in patients with relapsed or refractory diffuse large B-cell lymphoma. Clin Cancer Res. 2017 Aug 1;23(15):4127-4137. Epub 2017 Apr 5. [http://clincancerres.aacrjournals.org/content/23/15/4127.long link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28381416 PubMed] EudraCT 2009-013483-38
 
−
==Gemcitabine & Rituximab {{#subobject:1ba986|Regimen=1}}==
 
−
R-G: '''<u>R</u>'''ituximab & '''<u>G</u>'''emcitabine
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 6 cycles maximum {{#subobject:cd268h|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.16255 Pettengell et al. 2019 (PIX306)]
 
−
|2011-2018
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Stub#Pixantrone_.26_Rituximab|Pixantrone & Rituximab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
'''28-day cycle for up to 6 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, indefinite {{#subobject:cd26f7|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6200343/ Dang et al. 2017 (B1931008)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Diffuse_large_B-cell_lymphoma_-_historical#R-INO|R-INO]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
**Cycle 2 onwards: 375 mg/m<sup>2</sup> IV once on day 1
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''B1931008:''' Dang NH, Ogura M, Castaigne S, Fayad LE, Jerkeman M, Radford J, Pezzutto A, Bondarenko I, Stewart DA, Shnaidman M, Sullivan S, Vandendries E, Tobinai K, Ramchandren R, Hamlin PA, Giné E, Ando K. Randomized, phase 3 trial of inotuzumab ozogamicin plus rituximab versus chemotherapy plus rituximab for relapsed/refractory aggressive B-cell non-Hodgkin lymphoma. Br J Haematol. 2018 Aug;182(4):583-586. Epub 2017 Jul 5. [https://doi.org/full/10.1111/bjh.14820 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6200343/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28677896 PubMed] NCT01232556
 
−
#'''PIX306:''' Pettengell R, Długosz-Danecka M, Andorsky D, Belada D, Georgiev P, Quick D, Singer JW, Singh SB, Pallis A, Egorov A, Salles G. Pixantrone plus rituximab versus gemcitabine plus rituximab in patients with relapsed aggressive B-cell non-Hodgkin lymphoma not eligible for stem cell transplantation: a phase 3, randomized, multicentre trial (PIX306). Br J Haematol. 2020 Jan;188(2):240-248. Epub 2019 Dec 27. [https://doi.org/10.1111/bjh.16255 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/31879945 PubMed] NCT01321541
 
−
==GVD {{#subobject:7102c5|Regimen=1}}==
 
−
GVD: '''<u>G</u>'''emcitabine, '''<u>V</u>'''inorelbine, '''<u>D</u>'''oxil (Pegylated liposomal doxorubicin)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:b6f37c|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://link.springer.com/article/10.1007/s12032-012-0350-5 Bai et al. 2013]
 
−
| style="background-color:#ffffbe" |Retrospective
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Gemcitabine (Gemzar)]] 800 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vinorelbine (Navelbine)]] 15 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Pegylated liposomal doxorubicin (Doxil)]] 20 mg/m<sup>2</sup> IV once on day 1
 
−
'''14-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''Retrospective:''' Bai B, Huang HQ, Cai QQ, Wang XX, Cai QC, Lin ZX, Gao Y, Xia Y, Bu Q, Guo Y. Promising long-term outcome of gemcitabine, vinorelbine, liposomal doxorubicin (GVD) in 14-day schedule as salvage regimen for patients with previously heavily treated Hodgkin's lymphoma and aggressive non-Hodgkin's lymphoma. Med Oncol. 2013 Mar;30(1):350. Epub 2013 Jan 18. [http://link.springer.com/article/10.1007/s12032-012-0350-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/23329307 PubMed]
 
−
==Ibritumomab tiuxetan protocol {{#subobject:0b97a2|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:5fd5b6|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/110/1/54.long Morschhauser et al. 2007]
 
−
|2001-2003
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''To be completed''
 
−
====Radioconjugate therapy====
 
−
*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin)]]
 
−
</div></div>
 
−
===References===
 
−
#Morschhauser F, Illidge T, Huglo D, Martinelli G, Paganelli G, Zinzani PL, Rule S, Liberati AM, Milpied N, Hess G, Stein H, Kalmus J, Marcus R. Efficacy and safety of yttrium-90 ibritumomab tiuxetan in patients with relapsed or refractory diffuse large B-cell lymphoma not appropriate for autologous stem-cell transplantation. Blood. 2007 Jul 1;110(1):54-8. Epub 2007 Mar 26. [http://www.bloodjournal.org/content/110/1/54.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/17387223 PubMed]
 
−
==Ibrutinib monotherapy {{#subobject:ba5ba9|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:f4ee96|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.nature.com/articles/nm.3884 Wilson et al. 2015 (PCYC-1106-CA)]
 
−
|2010-2012
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Clinically meaningful responses were observed in the ABC subtype, only. Further clinical trials are currently underway.''
 
−
====Targeted therapy====
 
−
*[[Ibrutinib (Imbruvica)]] 560 mg PO once per day
 
−
'''Continued indefinitely'''
 
−
</div></div>
 
−
===References===
 
−
<!-- # '''Abstract:''' Wyndham H. Wilson, MD, PhD, John F. Gerecitano, MD, PhD, Andre Goy, MD, Sven de Vos, MD, PhD, Vaishalee P. Kenkre, MD, Paul M. Barr, MD, Kristie A. Blum, MD, Andrei R. Shustov, MD, Ranjana H. Advani, MD, Jason Lih, PhD, Mickey Williams, PhD, Roland Schmitz, PhD, Yandan Yang, PhD, Stefania Pittaluga, MD, PhD, George Wright, PhD, Lori A. Kunkel, MD, Jesse McGreivy, MD, Sriram Balasubramanian, PhD, Mei Cheng, PhD, Davina Moussa, Joseph J. Buggy, PhD and Louis M. Staudt, MD, PhD. The Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib (PCI-32765), Has Preferential Activity in the ABC Subtype of Relapsed/Refractory De Novo Diffuse Large B-Cell Lymphoma (DLBCL): Interim Results of a Multicenter, Open-Label, Phase 2 Study. Blood 120, a686 (2012). [https://ash.confex.com/ash/2012/webprogram/Paper48270.html link to abstract] -->
 
−
#'''PCYC-1106-CA:''' Wilson WH, Young RM, Schmitz R, Yang Y, Pittaluga S, Wright G, Lih CJ, Williams PM, Shaffer AL, Gerecitano J, de Vos S, Goy A, Kenkre VP, Barr PM, Blum KA, Shustov A, Advani R, Fowler NH, Vose JM, Elstrom RL, Habermann TM, Barrientos JC, McGreivy J, Fardis M, Chang BY, Clow F, Munneke B, Moussa D, Beaupre DM, Staudt LM. Targeting B cell receptor signaling with ibrutinib in diffuse large B cell lymphoma. Nat Med. 2015 Aug;21(8):922-6. Epub 2015 Jul 20. [https://www.nature.com/articles/nm.3884 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26193343 PubMed] NCT00849654; NCT01325701
 
−
==Ifosfamide monotherapy {{#subobject:b9a669|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:cd9499|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1002/hon.2900090404 Case et al. 1991 (CALGB 8552)]
 
−
|NR
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(12)70212-7 Pettengell et al. 2012 (PIX301)]
 
−
|2004-2008
 
−
| style="background-color:#91cf61" |Phase 3, <20 pts in this arm (C)
 
−
|[[#Pixantrone_monotherapy|Pixantrone]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior CR/CRu rate
 
−
|-
 
−
|}
 
−
''Dose & schedule is as given in Pettengell et al. 2012. CALGB 8552 used a different dose & schedule. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.''
 
−
====Chemotherapy====
 
−
*[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup> IV once per day on days 1 & 2
 
−
====Supportive therapy====
 
−
*[[Mesna (Mesnex)]] dose not specified
 
−
'''28-day cycle for up to 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''CALGB 8552:''' Case DC Jr, Anderson J, Ervin TJ, Gottlieb A. Phase II trial of ifosfamide and mesna in previously treated patients with non-Hodgkin's lymphoma: Cancer and Leukemia Group B study 8552. Hematol Oncol. 1991 Jul-Oct;9(4-5):189-96. [https://doi.org/10.1002/hon.2900090404 link to original article] [https://pubmed.ncbi.nlm.nih.gov/1743622 PubMed]
 
−
#'''Review:''' Webb MS, Saltman DL, Connors JM, Goldie JH. A literature review of single agent treatment of multiply relapsed aggressive non-Hodgkin's lymphoma. Leuk Lymphoma. 2002 May;43(5):975-82.  [https://doi.org/10.1080/10428190290021632 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12148908 PubMed]
 
−
#'''PIX301:''' Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. [https://doi.org/10.1016/S1470-2045(12)70212-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22652183 PubMed] NCT00088530
 
−
==Lenalidomide monotherapy {{#subobject:f5ca0d|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, low dose {{#subobject:64ba17|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://clincancerres.aacrjournals.org/content/23/15/4127.long Czuczman et al. 2017 (DLC-001)]
 
−
|2009-2013
 
−
| style="background-color:#1a9851" |Phase 2/3 (E-switch-ooc)
 
−
|Investigator's choice of:<br> 1. [[#Etoposide_monotherapy|Etoposide]]<br> 2. [[#Gemcitabine_monotherapy|Gemcitabine]]<br> 3. [[#Oxaliplatin_monotherapy|Oxaliplatin]]<br> 4. [[#Rituximab_monotherapy_3|Rituximab]]
 
−
| style="background-color:#d9ef8b" |Might have superior ORR
 
−
|-
 
−
|}
 
−
''Note: This dose was intended for patients with CrCl at least 30 but less than 60 mL/min/1.73m<sup>2</sup>.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] 10 mg PO once per day on days 1 to 21
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, normal dose {{#subobject:7d5704|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2007.15.3429 Wiernik et al. 2008 (CC-5013-NHL-002)]
 
−
|2005-2006
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#8c6bb1" |ORR: 35%
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdq626 Witzig et al. 2011 (NHL-003)]
 
−
|2006-2008
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#8c6bb1" |ORR: 28%
 
−
|-
 
−
|[http://clincancerres.aacrjournals.org/content/23/15/4127.long Czuczman et al. 2017 (DLC-001)]
 
−
|2009-2013
 
−
| style="background-color:#1a9851" |Phase 2/3 (E-switch-ooc)
 
−
|Investigator's choice of:<br> 1. [[#Etoposide_monotherapy|Etoposide]]<br> 2. [[#Gemcitabine_monotherapy|Gemcitabine]]<br> 3. [[#Oxaliplatin_monotherapy|Oxaliplatin]]<br> 4. [[#Rituximab_monotherapy_3|Rituximab]]
 
−
| style="background-color:#d9ef8b" |Might have superior ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''CC-5013-NHL-002:''' Wiernik PH, Lossos IS, Tuscano JM, Justice G, Vose JM, Cole CE, Lam W, McBride K, Wride K, Pietronigro D, Takeshita K, Ervin-Haynes A, Zeldis JB, Habermann TM. Lenalidomide monotherapy in relapsed or refractory aggressive non-Hodgkin's lymphoma. J Clin Oncol. 2008 Oct 20;26(30):4952-7. Epub 2008 Jul 7. [https://doi.org/10.1200/jco.2007.15.3429 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18606983 PubMed] NCT00179660
 
−
#'''NHL-003:''' Witzig TE, Vose JM, Zinzani PL, Reeder CB, Buckstein R, Polikoff JA, Bouabdallah R, Haioun C, Tilly H, Guo P, Pietronigro D, Ervin-Haynes AL, Czuczman MS. An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma. Ann Oncol. 2011 Jul;22(7):1622-7. Epub 2011 Jan 12. [https://doi.org/10.1093/annonc/mdq626 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21228334 PubMed] NCT00413036
 
−
#'''DLC-001:''' Czuczman MS, Trněný M, Davies A, Rule S, Linton KM, Wagner-Johnston N, Gascoyne RD, Slack GW, Brousset P, Eberhard DA, Hernandez-Ilizaliturri FJ, Salles G, Witzig TE, Zinzani PL, Wright GW, Staudt LM, Yang Y, Williams PM, Lih CJ, Russo J, Thakurta A, Hagner P, Fustier P, Song D, Lewis ID. A phase 2/3 multicenter, randomized, open-label study to compare the efficacy and safety of lenalidomide versus investigator's choice in patients with relapsed or refractory diffuse large B-cell lymphoma. Clin Cancer Res. 2017 Aug 1;23(15):4127-4137. Epub 2017 Apr 5. [http://clincancerres.aacrjournals.org/content/23/15/4127.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28381416 PubMed] EudraCT 2009-013483-38
 
−
==Lenalidomide & Rituximab (R<sup>2</sup>) {{#subobject:d4c873|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, indefinite {{#subobject:a04708|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1038/leu.2013.95 Wang et al. 2013 (MDACC 2005-0461)]
 
−
|2008-2011
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] 20 mg PO once per day on days 1 to 21
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 4 cycles {{#subobject:ad1aa9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(11)00023-1 Zinzani et al. 2011 (REVLIRIT01)]
 
−
|2009
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] 20 mg PO once per day on days 1 to 21
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1 & 21
 
−
'''28-day cycle for 4 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*SD or better: [[#Lenalidomide_monotherapy_2|Lenalidomide]] maintenance
 
−
</div></div>
 
−
===References===
 
−
#'''REVLIRIT01:''' Zinzani PL, Pellegrini C, Gandolfi L, Stefoni V, Quirini F, Derenzini E, Broccoli A, Argnani L, Pileri S, Baccarani M. Combination of lenalidomide and rituximab in elderly patients with relapsed or refractory diffuse large B-cell lymphoma: a phase 2 trial. Clin Lymphoma Myeloma Leuk. 2011 Dec;11(6):462-6. Epub 2011 May 4. [http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(11)00023-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21859554 PubMed] NCT00968331
 
−
##'''Update:''' Zinzani PL, Pellegrini C, Derenzini E, Argnani L, Pileri S. Long-term efficacy of the combination of lenalidomide and rituximab in elderly relapsed/refractory diffuse large B-cell lymphoma patients. Hematol Oncol. 2013 Dec;31(4):223-4. Epub 2013 Apr 26. [https://doi.org/10.1002/hon.2049 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23620452 PubMed]
 
−
#'''MDACC 2005-0461:''' Wang M, Fowler N, Wagner-Bartak N, Feng L, Romaguera J, Neelapu SS, Hagemeister F, Fanale M, Oki Y, Pro B, Shah J, Thomas S, Younes A, Hosing C, Zhang L, Newberry KJ, Desai M, Cheng N, Badillo M, Bejarano M, Chen Y, Young KH, Champlin R, Kwak L, Fayad L. Oral lenalidomide with rituximab in relapsed or refractory diffuse large cell, follicular and transformed lymphoma: a phase II clinical trial. Leukemia. 2013 Sep;27(9):1902-9. Epub 2013 Apr 2. [https://doi.org/10.1038/leu.2013.95 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23545991 PubMed] NCT00294632
 
−
==Lenalidomide & Tafasitamab {{#subobject:d4abx3|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:737708|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/s1470-2045(20)30225-4 Salles et al. 2020 (L-MIND)]
 
−
|2016-2017
 
−
| style="background-color:#91cf61" |Phase 2 (RT)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] as follows:
 
−
**Cycles 1 to 12: 25 mg PO once per day on days 1 to 21
 
−
*[[Tafasitamab (Monjuvi)]] as follows:
 
−
**Cycle 1: 12 mg/kg IV over 2 hours once per day on days 1, 4, 8, 15, 22
 
−
**Cycles 2 & 3: 12 mg/kg IV over 2 hours once per day on days 1, 8, 15, 22
 
−
**Cycle 4 onwards: 12 mg/kg IV over 2 hours once per day on days 1 & 15
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- # '''Abstract:''' Kami J. Maddocks, Eva González Barca, Wojciech Jurczak, Anna Marina Liberati, Johannes Duell, Zsolt Nagy, Tomáš Papajík, Marc Andre, Nagesh Kalakonda, Martin H. Dreyling, Pier Luigi Zinzani, Sumeet Vijay Ambarkhane, Johannes Weirather, and Gilles A. Salles. L-mind: MOR208 combined with lenalidomide (LEN) in patients with relapsed or refractory diffuse large b-cell lymphoma (R-R DLBCL)—A single-arm phase II study. Journal of Clinical Oncology 2017 35:15_suppl, 7514-7514 [https://doi.org/10.1200/JCO.2017.35.15_suppl.7514 link to abstract] -->
 
−
# '''L-MIND:''' Salles G, Duell J, González Barca E, Tournilhac O, Jurczak W, Liberati AM, Nagy Z, Obr A, Gaidano G, André M, Kalakonda N, Dreyling M, Weirather J, Dirnberger-Hertweck M, Ambarkhane S, Fingerle-Rowson G, Maddocks K. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Lancet Oncol. 2020 Jul;21(7):978-988. Epub 2020 Jun 5. [https://doi.org/10.1016/s1470-2045(20)30225-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32511983 PubMed] NCT02399085
 
−
##'''Update:''' Duell J, Maddocks KJ, González-Barca E, Jurczak W, Liberati AM, De Vos S, Nagy Z, Obr A, Gaidano G, Abrisqueta P, Kalakonda N, André M, Dreyling M, Menne T, Tournilhac O, Augustin M, Rosenwald A, Dirnberger-Hertweck M, Weirather J, Ambarkhane S, Salles G. Long-term outcomes from the Phase II L-MIND study of tafasitamab (MOR208) plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma. Haematologica. 2021 Sep 1;106(9):2417-2426. [https://doi.org/10.3324/haematol.2020.275958 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8409029/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34196165/ PubMed]
 
−
==Lisocabtagene maraleucel monotherapy {{#subobject:6e6u14|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:6nvha6|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/s0140-6736(20)31366-0 Abramson et al. 2020 (TRANSCEND NHL-001)]
 
−
|2016-2019
 
−
| style="background-color:#91cf61" |Phase 1 (RT)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Lisocabtagene maraleucel (Breyanzi)]]
 
−
</div></div>
 
−
===References===
 
−
#'''TRANSCEND NHL-001:''' Abramson JS, Palomba ML, Gordon LI, Lunning MA, Wang M, Arnason J, Mehta A, Purev E, Maloney DG, Andreadis C, Sehgal A, Solomon SR, Ghosh N, Albertson TM, Garcia J, Kostic A, Mallaney M, Ogasawara K, Newhall K, Kim Y, Li D, Siddiqi T. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020 Sep 19;396(10254):839-852. Epub 2020 Sep 1. [https://doi.org/10.1016/s0140-6736(20)31366-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32888407 PubMed] NCT02631044
 
−
==Loncastuximab tesirine monotherapy {{#subobject:jgua99|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:jagix0|Variant=1}}===
 
−
{| class="wikitable sortable" style="color:white; background-color:#404040"
 
−
|<small>'''FDA-recommended dose'''</small>
 
−
|-
 
−
|}
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/s1470-2045(21)00139-x Caimi et al. 2021 (LOTIS-2)]
 
−
|2018-2019
 
−
| style="background-color:#91cf61" |Phase 2 (RT)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Antibody-drug conjugate therapy====
 
−
*[[Loncastuximab tesirine (Zynlonta)]] as follows:
 
−
**Cycles 1 & 2: 0.15 mg/kg IV over 30 minutes once on day 1
 
−
**Cycle 3 onwards: 0.075 mg/kg IV over 30 minutes once on day 1
 
−
====Supportive therapy====
 
−
*[[Dexamethasone (Decadron)]] 4 mg IV or PO twice per day on days -1 to 2 (3 days total)
 
−
'''21-day cycles for up to 18 cycles (1 year)'''
 
−
</div></div>
 
−
===References===
 
−
#'''LOTIS-2:''' Caimi PF, Ai W, Alderuccio JP, Ardeshna KM, Hamadani M, Hess B, Kahl BS, Radford J, Solh M, Stathis A, Zinzani PL, Havenith K, Feingold J, He S, Qin Y, Ungar D, Zhang X, Carlo-Stella C. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2021 Jun;22(6):790-800. Epub 2021 May 11. [https://doi.org/10.1016/s1470-2045(21)00139-x link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/33989558/ PubMed] NCT03589469
 
−
==Mitoxantrone monotherapy {{#subobject:6e3e59|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:b18da6|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://pubmed.ncbi.nlm.nih.gov/3282421 Bajetta et al. 1988a]
 
−
|NR in abstract
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Mitoxantrone (Novantrone)]] 14 mg/m<sup>2</sup> IV over 30 minutes once on day 1
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#Bajetta E, Buzzoni R, Valagussa P, Bonadonna G. Mitoxantrone: an active agent in refractory non-Hodgkin's lymphomas. Am J Clin Oncol. 1988 Apr;11(2):100-3. '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/3282421 PubMed]
 
−
#'''PIX301:''' Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. [https://doi.org/10.1016/S1470-2045(12)70212-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22652183 PubMed] NCT00088530
 
−
==Obinutuzumab monotherapy {{#subobject:9d2627|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:7475e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/119/22/5126.long Salles et al. 2012 (GAUGUIN)]
 
−
|2008-2009
 
−
| style="background-color:#91cf61" |Phase 1/2
 
−
|-
 
−
|}
 
−
''Note: this is the phase II dosing reported in Morschhauser et al. 2013.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Obinutuzumab (Gazyva)]] as follows:
 
−
**Cycle 1: 1600 mg (diluted to 10 mg/mL) IV once per day on days 1 & 8
 
−
**Cycles 2 to 8: 800 mg IV once on day 1
 
−
**Initial infusion rate is 50 mg/hour. In the absence of infusion-related reactions (IRRs), the rate is then increased by 50 mg/hour every 30 minutes, up to a maximum of 400 mg/hour.
 
−
====Supportive therapy====
 
−
*[[Acetaminophen (Tylenol)]] or paracetamol 650 to 1000 mg PO once per infusion, 30 minutes prior to [[Obinutuzumab (Gazyva)]]
 
−
*[[:Category:Antihistamines|"An antihistamine"]] once per infusion, 30 minutes prior to [[Obinutuzumab (Gazyva)]]
 
−
**If there were no infusion-related reactions (IRRs) requiring medication or infusion interruption, antihistamine could be omitted for subsequent infusions
 
−
*Premedication with [[:Category:Steroids|corticosteroids]] recommended for patients at high risk of infusion-related reactions (IRRs)
 
−
*Use of [[:Category:Granulocyte colony-stimulating factors|G-CSF]] allowed for severe neutropenia
 
−
*Antibiotic prophylaxis allowed
 
−
'''21-day cycle for 8 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''GAUGUIN:''' Salles G, Morschhauser F, Lamy T, Milpied N, Thieblemont C, Tilly H, Bieska G, Asikanius E, Carlile D, Birkett J, Pisa P, Cartron G. Phase 1 study results of the type II glycoengineered humanized anti-CD20 monoclonal antibody obinutuzumab (GA101) in B-cell lymphoma patients. Blood. 2012 May 31;119(22):5126-32. Epub 2012 Mar 19. [http://www.bloodjournal.org/content/119/22/5126.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/22431570 PubMed] NCT00517530
 
−
##'''Subgroup analysis:''' Morschhauser FA, Cartron G, Thieblemont C, Solal-Céligny P, Haioun C, Bouabdallah R, Feugier P, Bouabdallah K, Asikanius E, Lei G, Wenger M, Wassner-Fritsch E, Salles GA. Obinutuzumab (GA101) monotherapy in relapsed/refractory diffuse large B-cell lymphoma or mantle-cell lymphoma: results from the phase II GAUGUIN study. J Clin Oncol. 2013 Aug 10;31(23):2912-9. Epub 2013 Jul 8. [https://doi.org/10.1200/jco.2012.46.9585 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23835718 PubMed]
 
−
##'''Subgroup analysis:''' Salles GA, Morschhauser F, Solal-Céligny P, Thieblemont C, Lamy T, Tilly H, Gyan E, Lei G, Wenger M, Wassner-Fritsch E, Cartron G. Obinutuzumab (GA101) in patients with relapsed/refractory indolent non-Hodgkin lymphoma: results from the phase II GAUGUIN study. J Clin Oncol. 2013 Aug 10;31(23):2920-6. Epub 2013 Jul 8. [https://doi.org/10.1200/jco.2012.46.9718 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23835715 PubMed]
 
−
##'''Subgroup analysis:''' Cartron G, de Guibert S, Dilhuydy MS, Morschhauser F, Leblond V, Dupuis J, Mahe B, Bouabdallah R, Lei G, Wenger M, Wassner-Fritsch E, Hallek M. Obinutuzumab (GA101) in relapsed/refractory chronic lymphocytic leukemia: final data from the phase 1/2 GAUGUIN study. Blood. 2014 Oct 2;124(14):2196-202. Epub 2014 Aug 20. [http://www.bloodjournal.org/content/124/14/2196 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25143487 PubMed]
 
−
==Ofatumumab monotherapy {{#subobject:5ba252|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:4f5008|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.12537 Coiffier et al. 2013 (415 Study)]
 
−
|2007-NR
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Ofatumumab (Arzerra)]] as follows:
 
−
**Cycle 1: 300 mg IV once on day 1, then 1000 mg IV once per day on days 8, 15, 22
 
−
**Cycle 2: 1000 mg IV once per day on days 1, 8, 15, 22
 
−
====Supportive therapy====
 
−
*[[Acetaminophen (Tylenol)]] (or equivalent) 1000 mg PO once per day on days 1, 8, 15, 22; 30 minutes to 2 hours prior to [[Ofatumumab (Arzerra)]]
 
−
*[[Cetirizine (Zyrtec)]] (or equivalent) 10 mg PO once per day on days 1, 8, 15, 22; 30 minutes to 2 hours prior to [[Ofatumumab (Arzerra)]]
 
−
*[[Prednisolone (Millipred)]] (or equivalent) 100 mg (route not specified) once per day on days 1 & 8; 30 minutes to 2 hours prior to [[Ofatumumab (Arzerra)]] for first 2 infusions, only
 
−
'''28-day cycle for 2 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''415 Study:''' Coiffier B, Radford J, Bosly A, Martinelli G, Verhoef G, Barca G, Davies A, Decaudin D, Gallop-Evans E, Padmanabhan-Iyer S, Van Eygen K, Wu KL, Gupta IV, Lin TS, Goldstein N, Jewell RC, Winter P, Lisby S; 415 study investigators. A multicentre, phase II trial of ofatumumab monotherapy in relapsed/progressive diffuse large B-cell lymphoma. Br J Haematol. 2013 Nov;163(3):334-42. Epub 2013 Aug 23. [https://doi.org/10.1111/bjh.12537 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24032456 PubMed] NCT00622388
 
−
==Oxaliplatin monotherapy {{#subobject:308526|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 100 mg/m<sup>2</sup> {{#subobject:1fc8c3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1023/a:1008310708853 Germann et al. 1999]
 
−
|1988-1994
 
−
| style="background-color:#ffffbe" |Phase 2, <20 pts in this subgroup
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(12)70212-7 Pettengell et al. 2012 (PIX301)]
 
−
|2004-2008
 
−
| style="background-color:#91cf61" |Phase 3, <20 pts in this arm (C)
 
−
|[[#Pixantrone_monotherapy|Pixantrone]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior CR/CRu rate
 
−
|-
 
−
|[http://clincancerres.aacrjournals.org/content/23/15/4127.long Czuczman et al. 2017 (DLC-001)]
 
−
|2009-2013
 
−
| style="background-color:#1a9851" |Phase 2/3 (C)
 
−
|[[#Lenalidomide_monotherapy_3|Lenalidomide]]
 
−
| style="background-color:#fee08b" |Might have inferior ORR
 
−
|-
 
−
|}
 
−
''Germann et al. give a range of 100 to 130 mg/m<sup>2</sup>. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.''
 
−
====Chemotherapy====
 
−
*[[Oxaliplatin (Eloxatin)]] 100 mg/m<sup>2</sup> IV once on day 1
 
−
'''21-day cycles (maximum of 6 cycles in PIX301 & DLC-001)'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 130 mg/m<sup>2</sup> {{#subobject:1bc18a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1023/a:1008310708853 Germann et al. 1999]
 
−
|1988-1994
 
−
| style="background-color:#ffffbe" |Phase 2, <20 pts in this subgroup
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1002/cncr.21219 Oki et al. 2005]
 
−
|2001-2003
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#8c6bb1" |ORR: 27% (95% CI, 13–47)
 
−
|-
 
−
|}
 
−
''Germann et al. give a range of 100 to 130 mg/m<sup>2</sup>.''
 
−
====Chemotherapy====
 
−
*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#Germann N, Brienza S, Rotarski M, Emile JF, Di Palma M, Musset M, Reynes M, Soulié P, Cvitkovic E, Misset JL. Preliminary results on the activity of oxaliplatin (L-OHP) in refractory/recurrent non-Hodgkin's lymphoma patients. Ann Oncol. 1999 Mar;10(3):351-4. [https://doi.org/10.1023/a:1008310708853 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10355582 PubMed]
 
−
#'''Review:''' Webb MS, Saltman DL, Connors JM, Goldie JH. A literature review of single agent treatment of multiply relapsed aggressive non-Hodgkin's lymphoma. Leuk Lymphoma. 2002 May;43(5):975-82.  [https://doi.org/10.1080/10428190290021632 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12148908 PubMed]
 
−
#Oki Y, McLaughlin P, Pro B, Hagemeister FB, Bleyer A, Loyer E, Younes A. Phase II study of oxaliplatin in patients with recurrent or refractory non-Hodgkin lymphoma. Cancer. 2005 Aug 15;104(4):781-7. [https://doi.org/10.1002/cncr.21219 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15973667 PubMed]
 
−
#'''PIX301:''' Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. [https://doi.org/10.1016/S1470-2045(12)70212-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22652183 PubMed] NCT00088530
 
−
#'''DLC-001:''' Czuczman MS, Trněný M, Davies A, Rule S, Linton KM, Wagner-Johnston N, Gascoyne RD, Slack GW, Brousset P, Eberhard DA, Hernandez-Ilizaliturri FJ, Salles G, Witzig TE, Zinzani PL, Wright GW, Staudt LM, Yang Y, Williams PM, Lih CJ, Russo J, Thakurta A, Hagner P, Fustier P, Song D, Lewis ID. A phase 2/3 multicenter, randomized, open-label study to compare the efficacy and safety of lenalidomide versus investigator's choice in patients with relapsed or refractory diffuse large B-cell lymphoma. Clin Cancer Res. 2017 Aug 1;23(15):4127-4137. Epub 2017 Apr 5. [http://clincancerres.aacrjournals.org/content/23/15/4127.long link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28381416 PubMed] EudraCT 2009-013483-38
 
−
==Panobinostat monotherapy {{#subobject:6b0341|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:d71d7c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972610/ Assouline et al. 2016 (Q-CROC-02)]
 
−
|2010-2013
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-de-esc)
 
−
|[[#Panobinostat_.26_Rituximab|Panobinostat & Rituximab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|}
 
−
''Note: patients had a median of 2 prior treatments (range 1-8).''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Panobinostat (Farydak)]] 30 mg PO three times per week (e.g., MWF)
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''Q-CROC-02:''' Assouline SE, Nielsen TH, Yu S, Alcaide M, Chong L, MacDonald D, Tosikyan A, Kukreti V, Kezouh A, Petrogiannis-Haliotis T, Albuquerque M, Fornika D, Alamouti S, Froment R, Greenwood CM, Oros KK, Camglioglu E, Sharma A, Christodoulopoulos R, Rousseau C, Johnson N, Crump M, Morin RD, Mann KK. Phase 2 study of panobinostat with or without rituximab in relapsed diffuse large B-cell lymphoma. Blood. 2016 Jul 14;128(2):185-94. Epub 2016 May 10. [http://www.bloodjournal.org/content/128/2/185.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972610/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27166360 PubMed] NCT01238692
 
−
==Panobinostat & Rituximab {{#subobject:f7bdff|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:cc78db|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972610/ Assouline et al. 2016 (Q-CROC-02)]
 
−
|2010-2013
 
−
| style="background-color:#91cf61" |Randomized Phase 2, <20 pts (E-esc)
 
−
|[[#Panobinostat_monotherapy|Panobinostat]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|}
 
−
''Note: patients had a median of 3 prior treatments (range 2-9).''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Panobinostat (Farydak)]] 30 mg PO three times per week (e.g., MWF)
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''Q-CROC-02:''' Assouline SE, Nielsen TH, Yu S, Alcaide M, Chong L, MacDonald D, Tosikyan A, Kukreti V, Kezouh A, Petrogiannis-Haliotis T, Albuquerque M, Fornika D, Alamouti S, Froment R, Greenwood CM, Oros KK, Camglioglu E, Sharma A, Christodoulopoulos R, Rousseau C, Johnson N, Crump M, Morin RD, Mann KK. Phase 2 study of panobinostat with or without rituximab in relapsed diffuse large B-cell lymphoma. Blood. 2016 Jul 14;128(2):185-94. Epub 2016 May 10. [http://www.bloodjournal.org/content/128/2/185.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972610/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27166360 PubMed] NCT01238692
 
−
==Pixantrone monotherapy {{#subobject:bedd78|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:7fef70|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(12)70212-7 Pettengell et al. 2012 (PIX301)]
 
−
|2004-2008
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|Investigator's choice of:<br> 1. [[#Etoposide_monotherapy|Etoposide]]<br> 2. [[#Gemcitabine_monotherapy|Gemcitabine]]<br> 3. [[#Ifosfamide_monotherapy|Ifosfamide]]<br> 4. [[#Mitoxantrone_monotherapy|Mitoxantrone]]<br> 5. [[#Oxaliplatin_monotherapy|Oxaliplatin]]<br> 6. [[#Vinorelbine_monotherapy|Vinorelbine]]
 
−
| style="background-color:#91cf60" |Seems to have superior CR/CRu rate
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Pixantrone (Pixuvri)]] 85 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
'''28-day cycle for up to 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''PIX301:''' Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. [https://doi.org/10.1016/S1470-2045(12)70212-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22652183 PubMed] NCT00088530
 
−
##'''Post-hoc analysis:''' Pettengell R, Sebban C, Zinzani PL, Derigs HG, Kravchenko S, Singer JW, Theocharous P, Wang L, Pavlyuk M, Makhloufi KM, Coiffier B. Monotherapy with pixantrone in histologically confirmed relapsed or refractory aggressive B-cell non-Hodgkin lymphoma: post-hoc analyses from a phase III trial. Br J Haematol. 2016 Sep;174(5):692-9. Epub 2016 Apr 26. [https://doi.org/10.1111/bjh.14101 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5074333/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27118109 PubMed]
 
−
==Rituximab monotherapy {{#subobject:d826ec|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:99a6d0|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/92/6/1927.long Coiffier et al. 1998]
 
−
|1996-1997
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-de-esc)
 
−
|[[#Rituximab_monotherapy_3|Rituximab]]; higher-dose
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|[http://clincancerres.aacrjournals.org/content/23/15/4127.long Czuczman et al. 2017 (DLC-001)]
 
−
|2009-2013
 
−
| style="background-color:#1a9851" |Phase 2/3 (C)
 
−
|[[#Lenalidomide_monotherapy_3|Lenalidomide]]
 
−
| style="background-color:#fee08b" |Might have inferior ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
**Cycles 4, 6, 8, 10: 375 mg/m<sup>2</sup> IV once on day 1
 
−
'''28-day cycle for 10 cycles (8 doses total)'''
 
−
</div></div>
 
−
===References===
 
−
#Coiffier B, Haioun C, Ketterer N, Engert A, Tilly H, Ma D, Johnson P, Lister A, Feuring-Buske M, Radford JA, Capdeville R, Diehl V, Reyes F. Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma: a multicenter phase II study. Blood. 1998 Sep 15;92(6):1927-32. [http://www.bloodjournal.org/content/92/6/1927.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/9731049 PubMed]
 
−
#'''DLC-001:''' Czuczman MS, Trněný M, Davies A, Rule S, Linton KM, Wagner-Johnston N, Gascoyne RD, Slack GW, Brousset P, Eberhard DA, Hernandez-Ilizaliturri FJ, Salles G, Witzig TE, Zinzani PL, Wright GW, Staudt LM, Yang Y, Williams PM, Lih CJ, Russo J, Thakurta A, Hagner P, Fustier P, Song D, Lewis ID. A phase 2/3 multicenter, randomized, open-label study to compare the efficacy and safety of lenalidomide versus investigator's choice in patients with relapsed or refractory diffuse large B-cell lymphoma. Clin Cancer Res. 2017 Aug 1;23(15):4127-4137. Epub 2017 Apr 5. [http://clincancerres.aacrjournals.org/content/23/15/4127.long link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28381416 PubMed] EudraCT 2009-013483-38
 
−
==R-BL {{#subobject:fe578a|Regimen=1}}==
 
−
R-BL: '''<u>R</u>'''ituximab, '''<u>B</u>'''endamustine, '''<u>L</u>'''enalidomide
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:f063a7|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.14049 Hitz et al. 2016 (SAKK 38/08)]
 
−
|NR
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|ORR: 61% (95% CI 45-76%)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Lenalidomide (Revlimid)]] 10 mg PO once per day on days 1 to 21
 
−
====Chemotherapy====
 
−
*[[Bendamustine]] 70 mg/m<sup>2</sup> IV once per day on days 1 & 2
 
−
'''28-day cycle for 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''SAKK 38/08:''' Hitz F, Zucca E, Pabst T, Fischer N, Cairoli A, Samaras P, Caspar CB, Mach N, Krasniqi F, Schmidt A, Rothermundt C, Enoiu M, Eckhardt K, Berardi Vilei S, Rondeau S, Mey U. Rituximab, bendamustine and lenalidomide in patients with aggressive B-cell lymphoma not eligible for anthracycline-based therapy or intensive salvage chemotherapy - SAKK 38/08. Br J Haematol. 2016 Jul;174(2):255-63. Epub 2016 Mar 28. [https://doi.org/10.1111/bjh.14049 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27018242 PubMed] NCT00987493
 
−
==R-CVEP {{#subobject:cea36|Regimen=1}}==
 
−
R-CVEP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''orinostat, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:d9b3c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.13195 Straus et al. 2014 (MSK 08-045)]
 
−
|2008-2012
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''The MTD for vorinostat was 300 mg in this phase I/II trial.''
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Vorinostat (Zolinza)]] 300 mg PO once per day on days 1 to 10
 
−
====Chemotherapy====
 
−
*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Etoposide (Vepesid)]] 70 mg/m<sup>2</sup> IV once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO once per day on days 1 to 10
 
−
'''28-day cycle for 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''MSK 08-045:''' Straus DJ, Hamlin PA, Matasar MJ, Lia Palomba M, Drullinsky PR, Zelenetz AD, Gerecitano JF, Noy A, Hamilton AM, Elstrom R, Wegner B, Wortman K, Cella D. Phase I/II trial of vorinostat with rituximab, cyclophosphamide, etoposide and prednisone as palliative treatment for elderly patients with relapsed or refractory diffuse large B-cell lymphoma not eligible for autologous stem cell transplantation. Br J Haematol. 2015 Mar;168(5):663-70. Epub 2014 Oct 15. [https://doi.org/10.1111/bjh.13195 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25316653 PubMed] NCT00667615
 
−
==R-GemOx {{#subobject:bb9813|Regimen=1}}==
 
−
R-GemOx: '''<u>R</u>'''ituximab, '''<u>Gem</u>'''citabine, '''<u>Ox</u>'''aliplatin
 
−
GEMOX-R: '''<u>GEM</u>'''citabine, '''<u>OX</u>'''aliplatin, '''<u>R</u>'''ituximab
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 14-day cycles {{#subobject:a875bf|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdm133 El Gnaoui et al. 2007]
 
−
|2002-2005
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3815173/ Mounier et al. 2013]
 
−
|2003-2009
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV at fixed dose rate over 100 minutes once on day 2
 
−
*[[Oxaliplatin (Eloxatin)]] 100 mg/m<sup>2</sup> IV over 2 hours once on day 2
 
−
====Supportive therapy====
 
−
*[[Methylprednisolone (Solumedrol)]] 1 mg/kg IV once on day 1, prior to [[Rituximab (Rituxan)]]
 
−
*[[Acetaminophen (Tylenol)]] 1000 mg PO once on day 1, prior to [[Rituximab (Rituxan)]]
 
−
*[[Dexchlorpheniramine (Polaramine)]] 6 mg PO once on day 1, prior to [[Rituximab (Rituxan)]]
 
−
*Primary prophylaxis with G-CSF was not permitted
 
−
'''14-day cycle for up to 8 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 21-day cycles {{#subobject:b976d9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1111/j.1600-0609.2007.00996.x López et al. 2008]
 
−
|NR in abstract
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy====
 
−
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Oxaliplatin (Eloxatin)]] 100 mg/m<sup>2</sup> IV once on day 1
 
−
'''21-day cycle for 6 to 8 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#El Gnaoui T, Dupuis J, Belhadj K, Jais JP, Rahmouni A, Copie-Bergman C, Gaillard I, Diviné M, Tabah-Fisch I, Reyes F, Haioun C. Rituximab, gemcitabine and oxaliplatin: an effective salvage regimen for patients with relapsed or refractory B-cell lymphoma not candidates for high-dose therapy. Ann Oncol. 2007 Aug;18(8):1363-8. Epub 2007 May 11. [https://doi.org/10.1093/annonc/mdm133 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17496309 PubMed]
 
−
#López A, Gutiérrez A, Palacios A, Blancas I, Navarrete M, Morey M, Perelló A, Alarcón J, Martínez J, Rodríguez J. GEMOX-R regimen is a highly effective salvage regimen in patients with refractory/relapsing diffuse large-cell lymphoma: a phase II study. Eur J Haematol. 2008 Feb;80(2):127-32. Epub 2007 Nov 20. [https://doi.org/10.1111/j.1600-0609.2007.00996.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18005385 PubMed]
 
−
#Mounier N, El-Gnaoui T, Tilly H, Canioni D, Sebban C, Casasnovas RO, Delarue R, Sonet A, Beaussart P, Petrella T, Castaigne S, Bologna S, Salles G, Rahmouni A, Gaulard P, Haioun C. Rituximab plus gemcitabine and oxaliplatin in refractory/relapsed patients with diffuse large B-cell lymphoma who are not candidates for high-dose therapy: a phase II Lymphoma Study Association trial. Haematologica. 2013 Nov;98(11):1726-31. Epub 2013 Jun 10. [http://www.haematologica.org/content/98/11/1726.full link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3815173/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23753028 PubMed] NCT00169195
 
−
==Selinexor monotherapy {{#subobject:d68g71|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:y42c19|Variant=1}}===
 
−
{| class="wikitable" style="color:white; background-color:#404040"
 
−
|<small>'''FDA-recommended dose'''</small>
 
−
|-
 
−
|}
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/s2352-3026(20)30120-4 Kalakonda et al. 2020 (SADAL)]
 
−
|2015-2019
 
−
| style="background-color:#91cf61" |Phase 2b (RT)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Selinexor (Xpovio)]] 60 mg PO once per day on days 1 & 3
 
−
'''7-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''SADAL:''' Kalakonda N, Maerevoet M, Cavallo F, Follows G, Goy A, Vermaat JSP, Casasnovas O, Hamad N, Zijlstra JM, Bakhshi S, Bouabdallah R, Choquet S, Gurion R, Hill B, Jaeger U, Sancho JM, Schuster M, Thieblemont C, De la Cruz F, Egyed M, Mishra S, Offner F, Vassilakopoulos TP, Warzocha K, McCarthy D, Ma X, Corona K, Saint-Martin JR, Chang H, Landesman Y, Joshi A, Wang H, Shah J, Shacham S, Kauffman M, Van Den Neste E, Canales MA. Selinexor in patients with relapsed or refractory diffuse large B-cell lymphoma (SADAL): a single-arm, multinational, multicentre, open-label, phase 2 trial. Lancet Haematol. 2020 Jul;7(7):e511-e522. [https://doi.org/10.1016/s2352-3026(20)30120-4 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/32589977/ PubMed] NCT02227251
 
−
==Temsirolimus monotherapy {{#subobject:4baa29|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:21e303|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|Years of enrollment
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020703/ Smith et al. 2010 (NCI-6199)]
 
−
|2004-NR
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#8c6bb1" |ORR: 28%
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Temsirolimus (Torisel)]] 25 mg IV over 30 minutes once per day on days 1, 8, 15, 22
 
−
'''28-day cycle for up to 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''NCI-6199:''' Smith SM, van Besien K, Karrison T, Dancey J, McLaughlin P, Younes A, Smith S, Stiff P, Lester E, Modi S, Doyle LA, Vokes EE, Pro B. Temsirolimus has activity in non-mantle cell non-Hodgkin's lymphoma subtypes: The University of Chicago phase II consortium. J Clin Oncol. 2010 Nov 1;28(31):4740-6. Epub 2010 Sep 13. [https://doi.org/10.1200/jco.2010.29.2813 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020703/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20837940 PubMed] NCT00290472
 
−
==Tisagenlecleucel monotherapy {{#subobject:d68f14|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:60fc19|Variant=1}}===
 
−
{| class="wikitable" style="color:white; background-color:#404040"
 
−
|<small>'''FDA-recommended dose'''</small>
 
−
|-
 
−
|}
 
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 
−
! style="width: 25%" |Study
 
−
! style="width: 25%" |Years of enrollment
 
−
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 25%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5788566/ Schuster et al. 2017 (UPCC 13413)]
 
−
|2014-2016
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa1804980 Schuster et al. 2018 (JULIET)]
 
−
|2015-2017
 
−
| style="background-color:#91cf61" |Phase 2 (RT)
 
−
| style="background-color:#9ebcda" |ORR: 59% (95% CI, 44-72)
 
−
|-
 
−
|}
 
−
''The range given is the FDA-recommended dose used in JULIET.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*Lymphodepleting therapy with [[Autologous_HSCT#FC|FC]] or [[Autologous_HSCT#Bendamustine_monotherapy|Bendamustine]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Tisagenlecleucel (Kymriah)]] 0.6 to 6 x 10<sup>8</sup> CTL019 transduced viable T-cells IV once on day 0
 
−
'''One course'''
 
−
</div></div>
 
−
===References===
 
−
#'''UPCC 13413:''' Schuster SJ, Svoboda J, Chong EA, Nasta SD, Mato AR, Anak Ö, Brogdon JL, Pruteanu-Malinici I, Bhoj V, Landsburg D, Wasik M, Levine BL, Lacey SF, Melenhorst JJ, Porter DL, June CH. Chimeric Antigen Receptor T Cells in Refractory B-Cell Lymphomas. N Engl J Med. 2017 Dec 28;377(26):2545-2554. Epub 2017 Dec 10. [https://doi.org/10.1056/NEJMoa1708566 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5788566/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29226764 PubMed] NCT02030834
 
−
<!-- # '''Abstract:''' Schuster SJ, Bishop MR, Tam C, et al. Global Pivotal Phase 2 Trial of the CD19-Targeted Therapy CTL019 in Adult Patients with Relapsed or Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)—an Interim Analysis. Hematological Oncology. 2017;35(S2):27. [https://doi.org/full/10.1002/hon.2437_6 link to abstract] -->
 
−
#'''JULIET:''' Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, Jäger U, Jaglowski S, Andreadis C, Westin JR, Fleury I, Bachanova V, Foley SR, Ho PJ, Mielke S, Magenau JM, Holte H, Pantano S, Pacaud LB, Awasthi R, Chu J, Anak Ö, Salles G, Maziarz RT; JULIET Investigators. Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. N Engl J Med. 2019 Jan 3;380(1):45-56. Epub 2018 Dec 1.  [https://doi.org/10.1056/NEJMoa1804980 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30501490 PubMed] NCT02445248
 
−
##'''Update:''' Schuster SJ, Tam CS, Borchmann P, Worel N, McGuirk JP, Holte H, Waller EK, Jaglowski S, Bishop MR, Damon LE, Foley SR, Westin JR, Fleury I, Ho PJ, Mielke S, Teshima T, Janakiram M, Hsu JM, Izutsu K, Kersten MJ, Ghosh M, Wagner-Johnston N, Kato K, Corradini P, Martinez-Prieto M, Han X, Tiwari R, Salles G, Maziarz RT. Long-term clinical outcomes of tisagenlecleucel in patients with relapsed or refractory aggressive B-cell lymphomas (JULIET): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2021 Oct;22(10):1403-1415. Epub 2021 Sep 10. [https://doi.org/10.1016/s1470-2045(21)00375-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34516954/ PubMed]
 
−
==TTR {{#subobject:934c01|Regimen=1}}==
 
−
TTR: '''<u>T</u>'''axol (Paclitaxel), '''<u>T</u>'''opotecan, '''<u>R</u>'''ituximab
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:4882ef|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5279071/ Westin et al. 2014]
 
−
|1999-2003
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV once on day 2
 
−
*[[Topotecan (Hycamtin)]] 1 mg/m<sup>2</sup> IV once per day on days 2 to 6
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Supportive therapy====
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day from day 7 until neutrophil recovery
 
−
*[[Dexamethasone (Decadron)]] 20 mg IV once on day 2; 30 minutes prior to [[Paclitaxel (Taxol)]]
 
−
*[[Diphenhydramine (Benadryl)]] 50 mg IV once on day 2; 30 minutes prior to [[Paclitaxel (Taxol)]]
 
−
'''21-day cycle for up to 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#Westin JR, McLaughlin P, Romaguera J, Hagemeister FB, Pro B, Dang NH, Samaniego F, Rodriguez MA, Fayad L, Oki Y, Fanale M, Fowler N, Nastoupil L, Feng L, Loyer E, Younes A. Paclitaxel, topotecan and rituximab: long term outcomes of an effective salvage programme for relapsed or refractory aggressive B-cell non-Hodgkin lymphoma. Br J Haematol. 2014 Oct;167(2):177-84. Epub 2014 Jul 8. [https://doi.org/10.1111/bjh.13014 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5279071/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25039868 PubMed]
 
−
==Vinorelbine monotherapy {{#subobject:29c647|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:f0bd7f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/oxfordjournals.annonc.a010802 Balzarotti et al. 1996]
 
−
|1992-1994
 
−
| style="background-color:#ffffbe" |Non-randomized, <20 pts in this subgroup
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(12)70212-7 Pettengell et al. 2012 (PIX301)]
 
−
|2004-2008
 
−
| style="background-color:#91cf61" |Phase 3, <20 pts in this arm (C)
 
−
|[[#Pixantrone_monotherapy|Pixantrone]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior CR/CRu rate
 
−
|-
 
−
|}
 
−
''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
'''28-day cycle for up to 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#Balzarotti M, Santoro A, Tondini C, Fornier M, Bonadonna G. Activity of single agent vinorelbine in pretreated non-Hodgkin's lymphoma. Ann Oncol. 1996 Nov;7(9):970-2. [https://doi.org/10.1093/oxfordjournals.annonc.a010802 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9006750 PubMed]
 
−
#'''Review:''' Webb MS, Saltman DL, Connors JM, Goldie JH. A literature review of single agent treatment of multiply relapsed aggressive non-Hodgkin's lymphoma. Leuk Lymphoma. 2002 May;43(5):975-82.  [https://doi.org/10.1080/10428190290021632 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12148908 PubMed]
 
−
#'''PIX301:''' Pettengell R, Coiffier B, Narayanan G, de Mendoza FH, Digumarti R, Gomez H, Zinzani PL, Schiller G, Rizzieri D, Boland G, Cernohous P, Wang L, Kuepfer C, Gorbatchevsky I, Singer JW. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012 Jul;13(7):696-706. Epub 2012 May 30. Erratum in: Lancet Oncol. 2012 Jul;13(7):e285. [https://doi.org/10.1016/S1470-2045(12)70212-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22652183 PubMed] NCT00088530
 
−
##'''Post-hoc analysis:''' Pettengell R, Sebban C, Zinzani PL, Derigs HG, Kravchenko S, Singer JW, Theocharous P, Wang L, Pavlyuk M, Makhloufi KM, Coiffier B. Monotherapy with pixantrone in histologically confirmed relapsed or refractory aggressive B-cell non-Hodgkin lymphoma: post-hoc analyses from a phase III trial. Br J Haematol. 2016 Sep;174(5):692-9. Epub 2016 Apr 26. [https://doi.org/10.1111/bjh.14101 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5074333/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27118109 PubMed]
 
−
=Maintenance after further lines of therapy=
 
−
==Lenalidomide monotherapy {{#subobject:9ce5ad|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:829190|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(11)00023-1 Zinzani et al. 2011 (REVLIRIT01)]
 
−
|2009
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#Lenalidomide_.26_Rituximab_.28R2.29|Lenalidomide & Rituximab]] x 4
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Lenalidomide (Revlimid)]] 20 mg PO once per day on days 1 to 21
 
−
'''28-day cycle for 9 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''REVLIRIT01:''' Zinzani PL, Pellegrini C, Gandolfi L, Stefoni V, Quirini F, Derenzini E, Broccoli A, Argnani L, Pileri S, Baccarani M. Combination of lenalidomide and rituximab in elderly patients with relapsed or refractory diffuse large B-cell lymphoma: a phase 2 trial. Clin Lymphoma Myeloma Leuk. 2011 Dec;11(6):462-6. Epub 2011 May 4. [http://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(11)00023-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21859554 PubMed] NCT00968331
 
−
##'''Update:''' Zinzani PL, Pellegrini C, Derenzini E, Argnani L, Pileri S. Long-term efficacy of the combination of lenalidomide and rituximab in elderly relapsed/refractory diffuse large B-cell lymphoma patients. Hematol Oncol. 2013 Dec;31(4):223-4. Epub 2013 Apr 26. [https://doi.org/10.1002/hon.2049 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23620452 PubMed]
 
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=Response criteria=
 
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*[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979083/ Lugano Classification criteria (2014)] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979083/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25113753 PubMed]
 
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*[https://doi.org/10.1200/jco.2006.09.2403 International Harmonization Project on Lymphoma revised criteria (2007)] [https://pubmed.ncbi.nlm.nih.gov/17242396 PubMed]
 
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*[https://doi.org/10.1200/jco.1999.17.4.1244 NCI Sponsored International Working Group criteria (1999)] [https://pubmed.ncbi.nlm.nih.gov/10561185 PubMed]
 
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=Prognosis=
 
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==IPI and age-adjusted IPI (1993)==
 
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To be completed
 
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#A predictive model for aggressive non-Hodgkin's lymphoma. The International Non-Hodgkin's Lymphoma Prognostic Factors Project. N Engl J Med. 1993 Sep 30;329(14):987-94. [https://doi.org/10.1056/NEJM199309303291402 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8141877 PubMed]
 
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==Revised International Prognostic Index, R-IPI (2007)==
 
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To be completed
 
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#Sehn LH, Berry B, Chhanabhai M, Fitzgerald C, Gill K, Hoskins P, Klasa R, Savage KJ, Shenkier T, Sutherland J, Gascoyne RD, Connors JM. The revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP. Blood. 2007 Mar 1;109(5):1857-61. Epub 2006 Nov 14. [http://www.bloodjournal.org/content/109/5/1857.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/17105812 PubMed]
 
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==CNS-IPI (2016)==
 
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===Risk factors===
 
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*Age greater than 60 years
 
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*Elevated LDH
 
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*[[Performance_status#ECOG_performance_status_.28WHO.2FGOG.2FZubrod_score.29|ECOG PS]] greater than 1
 
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*Advanced stage (III or IV)
 
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*Involvement of more than one extranodal site
 
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*Involvement of the kidney and/or adrenal glands
 
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===Risk stratification===
 
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*'''Low risk:''' 0 or 1 risk factors (''2-year rate of CNS disease less than 5%'')
 
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*'''Intermediate risk:''' 2 or 3 risk factors (''2-year rate of CNS disease less than 5%'')
 
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*'''High risk:''' 4 to 6 risk factors (''2-year rate of CNS disease greater than 10%'')
 
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</div></div>
 
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===References===
 
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#Schmitz N, Zeynalova S, Nickelsen M, Kansara R, Villa D, Sehn LH, Glass B, Scott DW, Gascoyne RD, Connors JM, Ziepert M, Pfreundschuh M, Loeffler M, Savage KJ. CNS International Prognostic Index: a risk model for CNS relapse in patients with diffuse large B-cell lymphoma treated with R-CHOP. J Clin Oncol. 2016 Sep 10;34(26):3150-3156. Epub 2016 Jul 5. [https://doi.org/10.1200/jco.2015.65.6520 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27382100 PubMed]
 
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=Investigational agents=
 
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''These are drugs under study with at least some promising results for this disease.''
 
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*[[Coltuximab ravtansine (CoR, SAR3419)]]
 
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*[[Pidilizumab (CT-011)]]
 
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[[Category:Diffuse large B-cell lymphoma regimens]]
 
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[[Category:Disease-specific pages]]
 
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[[Category:Aggressive lymphomas]]
 
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[[Category:Non-Hodgkin lymphomas]]
 

Latest revision as of 00:13, 18 June 2023

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