Difference between revisions of "Staging page"

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[[#top|Back to Top]]
 
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{{#lst:Section editor transclusions|anhl}}
 
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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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''Note: these regimens have been studied specifically in primary mediastinal B-cell lymphoma. Other large B-cell lymphoma regimens, such as those used in [[diffuse large B-cell lymphoma]] are also often used.''
 
−
=Guidelines=
 
−
==BSH==
 
−
*'''2019:''' Cwynarski et al. [https://doi.org/10.1111/bjh.15731 The management of primary mediastinal B-cell lymphoma: a British Society for Haematology Good Practice Paper]
 
−
==[http://www.esmo.org/ ESMO]==
 
−
*'''2016:''' Vitolo et al. [http://annonc.oxfordjournals.org/content/27/suppl_5/v91.full.pdf+html Extranodal diffuse large B-cell lymphoma (DLBCL) and primary mediastinal B-cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/27377716 PubMed]
 
−
===Older===
 
−
*'''2013:''' [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]
 
−
=Untreated=
 
−
==DA-R-EPOCH {{#subobject:d7244e|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)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:98dcb9|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/pmc4568999/ Dunleavy et al. 2013 (NCI 93-C-0133)]
 
−
|1999-2012
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|[https://doi.org/10.1111/bjh.13273 Purroy et al. 2014]
 
−
|2002-2008
 
−
|style="background-color:#ffffbe"|Phase 2, <20 pts in this subgroup
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV over 3 hours once on day 1
 
−
====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>; dose was not capped)
 
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV over 2 hours 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====
 
−
*[[Filgrastim (Neupogen)]] 300 mcg SC once per day, starting on day 6 and continuing until ANC greater than 5,000/uL past nadir
 
−
*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] 160/800 mg (or equivalent if allergic) PO once per day on 3 days per week
 
−
**Note: It's assumed this is what the supplement for Dunleavy et al. 2013 meant by "Baxtrim (sulphametoxazole and trimethoprim)"
 
−
*[[Omeprazole (Prilosec)]] 20 mg (or equivalent) PO once per day
 
−
*[[Docusate (Colace)]] (dose not specified) and [[Sennosides (Senna)]] 2 tablets PO twice per day as needed for constipation
 
−
*Lactulose 20 g PO every 6 hours as needed for constipation
 
−
*Hepatitis B surface antigen positive patients received daily antiviral therapy until 8 weeks after completion of chemotherapy
 
−
'''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, increase etoposide, doxorubicin, and cyclophosphamide by one level (20%) compared to previous cycle.
 
−
*If nadir ANC less than 500, use same doses as last cycle.
 
−
*If nadir platelet count less than 25,000, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to the previous cycle.
 
−
</div></div>
 
−
===References===
 
−
# '''NCI 93-C-0133:''' Dunleavy K, Pittaluga S, Maeda LS, Advani R, Chen CC, Hessler J, Steinberg SM, Grant C, Wright G, Varma G, Staudt LM, Jaffe ES, Wilson WH. Dose-adjusted EPOCH-rituximab therapy in primary mediastinal B-cell lymphoma. N Engl J Med. 2013 Apr 11;368(15):1408-16. [https://doi.org/10.1056/NEJMoa1214561 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1214561/suppl_file/nejmoa1214561_appendix.pdf link to supplementary appendix] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4568999/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23574119 PubMed] NCT00001337
 
−
# 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. 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] [https://pubmed.ncbi.nlm.nih.gov/25521006 PubMed] EudraCT 2004-001684-22
 
−
==R-CHOP {{#subobject:796753|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
 
−
<br>CHOP-R
 
−
===Example orders===
 
−
*[[Example orders for R-CHOP in lymphoma]]
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:283715|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%2806%2970664-7 Pfreundschuh et al. 2006 (NCIC-CTG LY.9)]
 
−
|2000-2003
 
−
|style="background-color:#1a9851"|Phase 3 (E-esc)
 
−
|1. [[#CHOP_88|CHOP]]<br>2. [[#CHOEP_88|CHOEP]]<br> 3. [[#MACOP-B_88|MACOP-B]]<br> 4. [[#PMitCEBO_88|PMitCEBO]]
 
−
|style="background-color:#91cf60"|Seems to have superior 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)]] 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]]
 
−
</div></div>
 
−
===References===
 
−
# '''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]
 
−
## '''Subgroup analysis:''' Rieger M, Osterborg A, Pettengell R, White D, Gill D, Walewski J, Kuhnt E, Loeffler M, Pfreundschuh M, Ho AD; MabThera International Trial (MInT) Group. Primary mediastinal B-cell lymphoma treated with CHOP-like chemotherapy with or without rituximab: results of the Mabthera International Trial Group study. Ann Oncol. 2011 Mar;22(3):664-70. Epub 2010 Aug 19. [https://doi.org/10.1093/annonc/mdq418 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20724576 PubMed]
 
−
==R-CHOP (Prednisolone) {{#subobject:7a9c53|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 {{#subobject:74f424|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 (C)
 
−
|[[#R-CHOP-14_.28Prednisolone.29|R-CHOP-14]]
 
−
| style="background-color:#fee08b" |Might have inferior OS<sup>1</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on a post-hoc subgroup analysis.''
 
−
<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====
 
−
*[[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>
 
−
===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
 
−
## '''Subgroup analysis:''' Gleeson M, Hawkes EA, Cunningham D, Chadwick N, Counsell N, Lawrie A, Jack A, Smith P, Mouncey P, Pocock C, Ardeshna KM, Radford J, McMillan A, Davies J, Turner D, Kruger A, Johnson PW, Gambell J, Linch D. Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) in the management of primary mediastinal B-cell lymphoma: a subgroup analysis of the UK NCRI R-CHOP 14 versus 21 trial. Br J Haematol. 2016 Nov;175(4):668-672. Epub 2016 Aug 1. [https://onlinelibrary.wiley.com/wol1/doi/10.1111/bjh.14287 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27477167 PubMed]
 
−
==R-CHOP-14 (Prednisolone) {{#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>'''rednisolone every '''<u>14</u>''' days
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#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|R-CHOP-21]]
 
−
| style="background-color:#d9ef8b" |Might have superior OS<sup>1</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2016 subgroup analysis.''
 
−
<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====
 
−
*[[Prednisolone (Millipred)]] 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 6 cycles (8 cycles of rituximab)'''
 
−
</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
 
−
## '''Subgroup analysis:''' Gleeson M, Hawkes EA, Cunningham D, Chadwick N, Counsell N, Lawrie A, Jack A, Smith P, Mouncey P, Pocock C, Ardeshna KM, Radford J, McMillan A, Davies J, Turner D, Kruger A, Johnson PW, Gambell J, Linch D. Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) in the management of primary mediastinal B-cell lymphoma: a subgroup analysis of the UK NCRI R-CHOP 14 versus 21 trial. Br J Haematol. 2016 Nov;175(4):668-672. Epub 2016 Aug 1. [https://onlinelibrary.wiley.com/wol1/doi/10.1111/bjh.14287 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27477167 PubMed]
 
−
=Consolidation after upfront therapy=
 
−
==Radiation therapy {{#subobject:89ce8b|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:952fa4|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045%2806%2970664-7 Pfreundschuh et al. 2006 (NCIC-CTG LY.9)]
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[#CHOP|CHOP]] x 6 or [[#CHOEP-21|CHOEP-21]] x 6 or [[#PMitCEBO|PMitCEBO]] x 6 or [[#MACOP-B|MACOP-B]] x 6 versus [[#R-CHOP|R-CHOP]] x 6 or [[#R-CHOEP-21|R-CHOEP-21]] x 6 or [[#R-PMitCEBO|R-PMitCEBO]] x 6 or [[#R-MACOP-B|R-MACOP-B]] x 6
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Radiotherapy====
 
−
*[[External beam radiotherapy]]: 30 to 40 Gy given to sites of primary bulky disease; 30 to 40 Gy to primary extranodal disease at physician discretion
 
−
</div></div>
 
−
===References===
 
−
# '''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
 
−
## '''Subgroup analysis:''' Rieger M, Osterborg A, Pettengell R, White D, Gill D, Walewski J, Kuhnt E, Loeffler M, Pfreundschuh M, Ho AD; MabThera International Trial (MInT) Group. Primary mediastinal B-cell lymphoma treated with CHOP-like chemotherapy with or without rituximab: results of the Mabthera International Trial Group study. Ann Oncol. 2011 Mar;22(3):664-70. Epub 2010 Aug 19. [https://doi.org/10.1093/annonc/mdq418 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20724576 PubMed]
 
−
=Relapsed or refractory, salvage therapy=
 
−
==R-DHAP {{#subobject:26123c|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 {{#subobject:2ed78f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!Study
 
−
![[Levels_of_Evidence#Evidence|Evidence]]
 
−
!Comparator
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2013.53.9593 Crump et al. 2014 (NCIC-CTG LY.12)]
 
−
|style="background-color:#91cf61"|Phase 3, <20 pts in subgroup (C)
 
−
|[[Primary_mediastinal_B-cell_lymphoma#R-GDP|R-GDP]]
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 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
 
−
'''21-day cycle for up to 3 cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- 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
 
−
==R-GDP {{#subobject:f6075a|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 {{#subobject:8091c0|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!Study
 
−
![[Levels_of_Evidence#Evidence|Evidence]]
 
−
!Comparator
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2013.53.9593 Crump et al. 2014 (NCIC-CTG LY.12)]
 
−
|style="background-color:#91cf61"|Phase 3, <20 pts in subgroup (E-switch-ic)
 
−
|[[Primary_mediastinal_B-cell_lymphoma#R-DHAP|R-DHAP]]
 
−
|-
 
−
|}
 
−
<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>
 
−
===References===
 
−
<!-- 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
 
−
=Consolidation after salvage therapy=
 
−
==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" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(14)70161-5 Glass et al. 2014 (DSHNHL R3)]
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
{{#lst:Allogeneic HSCT|bfe434}}
 
−
</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
 
−
=Relapsed or refractory, further lines of therapy=
 
−
==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:#ffffbe"|Phase 1/2, <20 pts in subgroup (RT)
 
−
| style="background-color:#e0ecf4" |ORR: 82%
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*Lymphodepletion with [[Autologous_HSCT#FC|FC]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====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]
 
−
==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
 
−
==Pembrolizumab monotherapy {{#subobject:e0d17a|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:7b36e9|Variant=1}}===
 
−
{| class="wikitable" style="color:white; background-color:#404040"
 
−
|<small>'''FDA-recommended dose'''</small>
 
−
|-
 
−
|}
 
−
{| 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]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881098/ Armand et al. 2016 (KEYNOTE-013)]
 
−
|2014-2016
 
−
|style="background-color:#91cf61"|Phase 1b
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881098/ Armand et al. 2016 (KEYNOTE-170)]
 
−
|2016-2017
 
−
|style="background-color:#91cf61"|Phase 2 (RT)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Pembrolizumab (Keytruda)]] 200 mg IV over 30 minutes once on day 1
 
−
'''21-day cycle for up to 35 cycles (2 years)'''
 
−
</div></div>
 
−
===References===
 
−
<!-- # '''Abstract:''' J-M. Michot, P. Armand, W. Ding, V. Ribrag, B. Christian, A. Balakumaran, P. Marinello, S. Chlosta, Y. Zhang, M. Shipp, P.L. Zinzani; Pembrolizumab in patients with relapsed/refractory primary mediastinal large B-cell lymphoma (rrPMBCL) or relapsed or refractory Richter syndrome (rrRS): Phase 2 KEYNOTE-170 study, Annals of Oncology, Volume 27, Issue suppl_6, 1 October 2016, 944TiP. [https://academic.oup.com/annonc/article/27/suppl_6/944TiP/2799681 link to abstract] -->
 
−
# '''KEYNOTE-013:''' Armand P, Rodig S, Melnichenko V, Thieblemont C, Bouabdallah K, Tumyan G, Özcan M, Portino S, Fogliatto L, Caballero MD, Walewski J, Gulbas Z, Ribrag V, Christian B, Perini GF, Salles G, Svoboda J, Zain J, Patel S, Chen PH, Ligon AH, Ouyang J, Neuberg D, Redd R, Chatterjee A, Balakumaran A, Orlowski R, Shipp M, Zinzani PL. Pembrolizumab in Relapsed or Refractory Primary Mediastinal Large B-Cell Lymphoma. J Clin Oncol. 2019 Dec 1;37(34):3291-3299. Epub 2019 Oct 14. [https://doi.org/10.1200/JCO.19.01389 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881098/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31609651 PubMed] NCT01953692
 
−
# '''KEYNOTE-170:''' Armand P, Rodig S, Melnichenko V, Thieblemont C, Bouabdallah K, Tumyan G, Özcan M, Portino S, Fogliatto L, Caballero MD, Walewski J, Gulbas Z, Ribrag V, Christian B, Perini GF, Salles G, Svoboda J, Zain J, Patel S, Chen PH, Ligon AH, Ouyang J, Neuberg D, Redd R, Chatterjee A, Balakumaran A, Orlowski R, Shipp M, Zinzani PL. Pembrolizumab in Relapsed or Refractory Primary Mediastinal Large B-Cell Lymphoma. J Clin Oncol. 2019 Dec 1;37(34):3291-3299. Epub 2019 Oct 14. [https://doi.org/10.1200/JCO.19.01389 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881098/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31609651 PubMed] NCT02576990
 
−
[[Category:Primary mediastinal B-cell lymphoma regimens]]
 
−
[[Category:Disease-specific pages]]
 
−
[[Category:Aggressive lymphomas]]
 
−
[[Category:Non-Hodgkin lymphomas]]
 

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