Difference between revisions of "Staging page"

From HemOnc.org - A Hematology Oncology Wiki
Jump to navigation Jump to search
m
m
Line 6: Line 6:
 
{| class="wikitable" style="float:right; margin-right: 5px;"
 
{| class="wikitable" style="float:right; margin-right: 5px;"
 
|-
 
|-
−
|<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>
+
|<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>
−
<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>
+
<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>
 
|}
 
|}
 
{{TOC limit|limit=3}}
 
{{TOC limit|limit=3}}
−
''Transformed lymphoma, often referred to as Richter's transformation, most commonly arises from a preceding indolent lymphoma - usually [[Follicular lymphoma|follicular lymphoma]] or [[Chronic lymphocytic leukemia|chronic lymphocytic leukemia]]. It is typically treated as per the histologic subtype, which is usually [[Diffuse large B-cell lymphoma|DLBCL]]. However, some regimens specific to transformed lymphoma have been developed and are included here.''
+
''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.''
−
=All lines of therapy=
+
=Guidelines=
−
==Axicabtagene ciloleucel monotherapy {{#subobject:78231d|Regimen=1}}==
+
==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">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:e3e516|Variant=1}}===
+
===Regimen {{#subobject:98dcb9|Variant=1}}===
−
{| class="wikitable" style="color:white; background-color:#404040"
+
{| class="wikitable sortable" style="width: 60%; text-align:center;"
−
|<small>'''FDA-recommended dose'''</small>
+
!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)]
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"
+
|1999-2012
−
!style="width: 25%"|Study
+
|style="background-color:#91cf61"|Phase 2
−
!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)]
+
|[https://doi.org/10.1111/bjh.13273 Purroy et al. 2014]
−
|2015-2016
+
|2002-2008
−
|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]
 
−
==Bendamustine monotherapy {{#subobject:40b6d7|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:2806ae|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/10.1200/jco.2007.12.5070 Friedberg et al. 2008]
 
 
|style="background-color:#ffffbe"|Phase 2, <20 pts in this subgroup
 
|style="background-color:#ffffbe"|Phase 2, <20 pts in this subgroup
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<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====
 
====Chemotherapy====
−
*[[Bendamustine]] 120 mg/m<sup>2</sup> IV once per day on days 1 & 2
+
*[[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>)
−
'''21-day cycle for up to 12 cycles'''
+
*[[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>
 
</div></div>
 
===References===
 
===References===
−
<!-- Presented in part at the 48th Annual Meeting of the American Society of Hematology, December 9-12, 2006, Orlando, Florida -->
+
# '''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
−
# Friedberg JW, Cohen P, Chen L, Robinson KS, Forero-Torres A, La Casce AS, Fayad LE, Bessudo A, Camacho ES, Williams ME, van der Jagt RH, Oliver JW, Cheson BD. Bendamustine in patients with rituximab-refractory indolent and transformed non-Hodgkin's lymphoma: results from a phase II multicenter, single-agent study. J Clin Oncol. 2008 Jan 10;26(2):204-10. Erratum in: J Clin Oncol. 2008 Apr 10;26(11) 1911. [https://doi.org/10.1200/jco.2007.12.5070 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18182663 PubMed]
+
# 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
−
==<sup>131</sup>Iodine-Tositumomab monotherapy {{#subobject:4f79a4|Regimen=1}}==
+
==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">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:1c0cb9|Variant=1}}===
+
===Regimen {{#subobject:283715|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 20%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!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.2000.18.6.1316 Vose et al. 2000]
+
|[https://doi.org/10.1016/S1470-2045%2806%2970664-7 Pfreundschuh et al. 2006 (NCIC-CTG LY.9)]
−
|style="background-color:#91cf61"|Phase 2
+
|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]]
−
''Also evaluated in low-grade NHL but subtype was not specified. Now obsolete as this drug has been discontinued.''
+
|style="background-color:#91cf60"|Seems to have superior EFS
−
====Radioconjugate therapy, dosimetric step====
 
−
*On Day 0, infusions of:
 
−
**Tositumomab 450 mg IV over 1 hour
 
−
**[[Tositumomab and I-131 (Bexxar)|Tositumomab 35 mg labeled with 5 mCi of Iodine-131]] IV over 20 minutes
 
−
**First scan of whole body dosimetry & redistribution
 
−
*Day 2, 3, or 4: Second scan of whole body dosimetry & redistribution
 
−
*Day 6 or 7: Third scan of whole body dosimetry & redistribution
 
−
====Radioconjugate therapy, therapeutic step====
 
−
*Any day from day 7-14, infusions of:
 
−
**Tositumomab 450 mg IV over 1 hour
 
−
**[[Tositumomab and I-131 (Bexxar)|Tositumomab 35 mg labeled with an individually calculated dose of Iodine-131 that will provide 75 cGy of radiation to the total body]] IV over 20 minutes
 
−
***65 cGy total body dose used for patients with platelet counts of 100-150,000/mm3
 
−
''Calculated dose of I-131 is based on information from serial total-body gamma-camera counts''
 
−
</div></div>
 
−
===References===
 
−
# Vose JM, Wahl RL, Saleh M, Rohatiner AZ, Knox SJ, Radford JA, Zelenetz AD, Tidmarsh GF, Stagg RJ, Kaminski MS. Multicenter phase II study of iodine-131 tositumomab for chemotherapy-relapsed/refractory low-grade and transformed low-grade B-cell non-Hodgkin's lymphomas. J Clin Oncol. 2000 Mar;18(6):1316-23. [https://doi.org/10.1200/jco.2000.18.6.1316 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10715303 PubMed]
 
−
==Lenalidomide monotherapy {{#subobject:590ccf|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:87163f|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/10.1093/annonc/mdq626 Witzig et al. 2011 (NHL-003)]
 
−
|style="background-color:#91cf61"|Phase 2
 
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Targeted therapy====
 
====Targeted therapy====
−
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
−
'''28-day 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====
 +
*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>
 
</div></div>
 
===References===
 
===References===
−
# '''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
+
# '''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]
−
==Lenalidomide & Rituximab (R<sup>2</sup>) {{#subobject:cce1e0|Regimen=1}}==
+
## '''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">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:8347d9|Variant=1}}===
+
===Regimen {{#subobject:74f424|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 20%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!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/10.1038/leu.2013.95 Wang et al. 2013 (MDACC 2005-0461)]
+
|[https://doi.org/10.1016/S0140-6736(13)60313-X Cunningham et al. 2013 (UK NCRI R-CHOP14v21)]
−
|style="background-color:#ffffbe"|Phase 2, <20 pts in this subgroup
+
|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">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Targeted therapy====
 
====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 on day 1
−
*[[Rituximab (Rituxan)]] as follows:
+
====Chemotherapy====
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
+
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
−
'''28-day cycles'''
+
*[[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>
 
</div></div>
 
===References===
 
===References===
−
# '''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
+
# '''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
−
==Lenalidomide & Tafasitamab {{#subobject:d4abx3|Regimen=1}}==
+
## '''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">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:737708|Variant=1}}===
+
===Regimen {{#subobject:8136b1|Variant=1}}===
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 33%"|Study
+
!style="width: 20%"|Study
−
!style="width: 33%"|Years of enrollment
+
!style="width: 20%"|Years of enrollment
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!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(20)30225-4 Salles et al. 2020 (L-MIND)]
+
|[https://doi.org/10.1016/S0140-6736(13)60313-X Cunningham et al. 2013 (UK NCRI R-CHOP14v21)]
−
|2016-2017
+
|2005-2008
−
| style="background-color:#91cf61" |Phase 2 (RT)
+
|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">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Targeted therapy====
 
====Targeted therapy====
−
*[[Lenalidomide (Revlimid)]] as follows:
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
−
**Cycles 1 to 12: 25 mg PO once per day on days 1 to 21
+
====Chemotherapy====
−
*[[Tafasitamab (Monjuvi)]] as follows:
+
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
−
**Cycle 1: 12 mg/kg IV over 2 hours once per day on days 1, 4, 8, 15, 22
+
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
−
**Cycles 2 & 3: 12 mg/kg IV over 2 hours once per day on days 1, 8, 15, 22
+
*[[Vincristine (Oncovin)]] 2 mg IV once on day 1
−
**Cycle 4 onwards: 12 mg/kg IV over 2 hours once per day on days 1 & 15
+
====Glucocorticoid therapy====
−
'''28-day cycles'''
+
*[[Prednisolone (Millipred)]] 100 mg PO once per day on days 1 to 5
−
</div></div>
+
====CNS therapy, prophylaxis====
−
===References===
+
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:
−
<!-- # '''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] -->
+
*[[Methotrexate (MTX)]] 12.5 mg IT "for the first three cycles of treatment, administered as per local guidelines." No other details given.
−
# '''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
 
−
==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====
 
====Supportive therapy====
−
*[[Dexamethasone (Decadron)]] 4 mg IV or PO twice per day on days -1 to 2 (3 days total)
+
*[[Lenograstim (Granocyte)]] (dose/route not specified) given on days 4 to 12
−
'''21-day cycles for up to 18 cycles (1 year)'''
+
*[[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>
 
</div></div>
 
===References===
 
===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
+
# '''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
−
==OFAR {{#subobject:bd6061|Regimen=1}}==
+
## '''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]
−
OFAR: '''<u>O</u>'''xaliplatin, '''<u>F</u>'''ludarabine, '''<u>A</u>'''ra-C (Cytarabine), '''<u>R</u>'''ituximab
+
=Consolidation after upfront therapy=
 +
==Radiation therapy {{#subobject:89ce8b|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:bd771f|Variant=1}}===
+
===Regimen {{#subobject:952fa4|Variant=1}}===
−
{| class="wikitable sortable" style="width: 80%; text-align:center;"  
+
{| class="wikitable" style="width: 40%; text-align:center;"  
 
!style="width: 25%"|Study
 
!style="width: 25%"|Study
−
!style="width: 25%"|Years of enrollment
 
 
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|[https://doi.org/10.1200/jco.2007.11.8513 Tsimberidou et al. 2008]
+
|[https://doi.org/10.1016/S1470-2045%2806%2970664-7 Pfreundschuh et al. 2006 (NCIC-CTG LY.9)]
−
|2004-2006
+
| style="background-color:#91cf61" |Non-randomized portion of RCT
−
|style="background-color:#91cf61"|Phase 2
 
−
| style="background-color:#1a9850" |Likely has true ORR > 20%
 
−
|-
 
−
|}
 
−
''Note: the manuscript does not specify what sequence the rituximab is given in.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Oxaliplatin (Eloxatin)]] 25 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 4, '''given first (see note)'''
 
−
*[[Fludarabine (Fludara)]] 30 mg/m<sup>2</sup> IV once per day on days 2 & 3, '''given second, within 30 minutes of completion of oxaliplatin (see note)'''
 
−
*[[Cytarabine (Ara-C)]] 1000 mg/m<sup>2</sup> IV over 2 hours once per day on days 2 & 3, '''given third, 4 hours after start of fludarabine (see note)'''
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] as follows (see note):
 
−
**Cycle 1: 375 mg/m<sup>2</sup> IV over 4 to 6 hours once on day 3
 
−
**Cycles 2 to 6: 375 mg/m<sup>2</sup> IV over 4 to 6 hours once on day 1
 
−
====Supportive therapy====
 
−
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 6
 
−
*Herpes zoster and PCP (Pneumocystis jiroveci pneumonia) prophylaxis used
 
−
'''28-day cycle for up to 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
# Tsimberidou AM, Wierda WG, Plunkett W, Kurzrock R, O'Brien S, Wen S, Ferrajoli A, Ravandi-Kashani F, Garcia-Manero G, Estrov Z, Kipps TJ, Brown JR, Fiorentino A, Lerner S, Kantarjian HM, Keating MJ. Phase I-II study of oxaliplatin, fludarabine, cytarabine, and rituximab combination therapy in patients with Richter's syndrome or fludarabine-refractory chronic lymphocytic leukemia. J Clin Oncol. 2008 Jan 10;26(2):196-203. [https://doi.org/10.1200/jco.2007.11.8513 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/18182662 PubMed]
 
−
==Pembrolizumab monotherapy {{#subobject:1089ff|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:f10e64|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]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5492091/ Ding et al. 2017 (MC1485)]
 
−
|style="background-color:#ffffbe"|Phase 2, <20 pts in this subgroup
 
−
| style="background-color:#d9ef8b" |Unlikely to have true ORR > 20%
 
 
|-
 
|-
 
|}
 
|}
 +
<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">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Immunotherapy====
+
====Radiotherapy====
−
*[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1
+
*[[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
−
'''21-day cycle for up to 35 cycles (2 years)'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''MC1485:''' Ding W, LaPlant BR, Call TG, Parikh SA, Leis JF, He R, Shanafelt TD, Sinha S, Le-Rademacher J, Feldman AL, Habermann TM, Witzig TE, Wiseman GA, Lin Y, Asmus E, Nowakowski GS, Conte MJ, Bowen DA, Aitken CN, Van Dyke DL, Greipp PT, Liu X, Wu X, Zhang H, Secreto CR, Tian S, Braggio E, Wellik LE, Micallef I, Viswanatha DS, Yan H, Chanan-Khan AA, Kay NE, Dong H, Ansell SM. Pembrolizumab in patients with CLL and Richter transformation or with relapsed CLL. Blood. 2017 Jun 29;129(26):3419-3427. Epub 2017 Apr 19. [http://www.bloodjournal.org/content/129/26/3419.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5492091/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28424162 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
−
==R-DHAP {{#subobject:aacad1|Regimen=1}}==
+
## '''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)
 
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">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:482776|Variant=1}}===
+
===Regimen {{#subobject:2ed78f|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 20%"|Study
+
!Study
−
!style="width: 20%"|Years of enrollment
+
![[Levels_of_Evidence#Evidence|Evidence]]
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!Comparator
−
!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)]
 
|[https://doi.org/10.1200/jco.2013.53.9593 Crump et al. 2014 (NCIC-CTG LY.12)]
−
|2003-2011
+
|style="background-color:#91cf61"|Phase 3, <20 pts in subgroup (C)
−
|style="background-color:#1a9851"|Phase 3 (C)
+
|[[Primary_mediastinal_B-cell_lymphoma#R-GDP|R-GDP]]
−
|[[#R-GDP|R-GDP]]
 
−
|style="background-color:#d3d3d3"|Not reported
 
 
|-
 
|-
 
|}
 
|}
Line 290: Line 245:
 
<!-- 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. -->
 
<!-- 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
 
# '''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
−
## '''Subgroup Analysis:''' Kuruvilla J, MacDonald DA, Kouroukis CT, Cheung M, Olney HJ, Turner AR, Anglin P, Seftel M, Ismail WS, Luminari S, Couban S, Baetz T, Meyer RM, Hay AE, Shepherd L, Djurfeldt MS, Alamoudi S, Chen BE, Crump M. Salvage chemotherapy and autologous stem cell transplantation for transformed indolent lymphoma: a subset analysis of NCIC-CTG LY12. Blood. 2015 Aug 6;126(6):733-8. Epub 2015 Jun 24. [http://www.bloodjournal.org/content/126/6/733.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26109202 PubMed]
+
==R-GDP {{#subobject:f6075a|Regimen=1}}==
−
==R-EPOCH {{#subobject:86a128|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:51d707|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/10.1093/annonc/mdh093 Jermann et al. 2004]
 
−
|style="background-color:#ffffbe"|Phase 2, <20 pts in this subgroup
 
−
|-
 
−
|}
 
−
''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>
 
−
===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-GDP {{#subobject:8624f9|Regimen=1}}==
 
 
R-GDP: '''<u>R</u>'''ituximab, '''<u>G</u>'''emcitabine, '''<u>D</u>'''examethasone, '''<u>P</u>'''latinol (Cisplatin)
 
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">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:7e2222|Variant=1}}===
+
===Regimen {{#subobject:8091c0|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 20%"|Study
+
!Study
−
!style="width: 20%"|Years of enrollment
+
![[Levels_of_Evidence#Evidence|Evidence]]
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!Comparator
−
!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)]
 
|[https://doi.org/10.1200/jco.2013.53.9593 Crump et al. 2014 (NCIC-CTG LY.12)]
−
|2003-2011
+
|style="background-color:#91cf61"|Phase 3, <20 pts in subgroup (E-switch-ic)
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+
|[[Primary_mediastinal_B-cell_lymphoma#R-DHAP|R-DHAP]]
−
|[[#R-DHAP|R-DHAP]]
 
−
|style="background-color:#d3d3d3"|Not reported
 
 
|-
 
|-
 
|}
 
|}
Line 345: Line 268:
 
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
 
'''21-day cycle for up to 3 cycles'''
 
'''21-day cycle for up to 3 cycles'''
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*Responders: autologous HSCT
 
 
</div></div>
 
</div></div>
 
===References===
 
===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. -->
 
<!-- 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
 
# '''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
−
## '''Subgroup Analysis:''' Kuruvilla J, MacDonald DA, Kouroukis CT, Cheung M, Olney HJ, Turner AR, Anglin P, Seftel M, Ismail WS, Luminari S, Couban S, Baetz T, Meyer RM, Hay AE, Shepherd L, Djurfeldt MS, Alamoudi S, Chen BE, Crump M. Salvage chemotherapy and autologous stem cell transplantation for transformed indolent lymphoma: a subset analysis of NCIC-CTG LY12. Blood. 2015 Aug 6;126(6):733-8. Epub 2015 Jun 24. [http://www.bloodjournal.org/content/126/6/733.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26109202 PubMed]
+
=Consolidation after salvage therapy=
−
==Selinexor monotherapy {{#subobject:d68g71|Regimen=1}}==
+
==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">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:y42c19|Variant=1}}===
+
===Regimen {{#subobject:e3e516|Variant=1}}===
 
{| class="wikitable" style="color:white; background-color:#404040"
 
{| class="wikitable" style="color:white; background-color:#404040"
 
|<small>'''FDA-recommended dose'''</small>
 
|<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;"  
 
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
 
!style="width: 33%"|Study
 
!style="width: 33%"|Study
Line 366: Line 335:
 
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://doi.org/10.1016/s2352-3026(20)30120-4 Kalakonda et al. 2020 (SADAL)]
+
|[https://doi.org/10.1016/s0140-6736(20)31366-0 Abramson et al. 2020 (TRANSCEND NHL-001)]
−
|2015-2019
+
|2016-2019
−
| style="background-color:#91cf61" |Phase 2b (RT)
+
| style="background-color:#91cf61" |Phase 1 (RT)
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Targeted therapy====
+
====Immunotherapy====
−
*[[Selinexor (Xpovio)]] 60 mg PO once per day on days 1 & 3
+
*[[Lisocabtagene maraleucel (Breyanzi)]]
−
'''7-day cycles'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===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
+
#'''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
−
==Tisagenlecleucel monotherapy {{#subobject:d68f14|Regimen=1}}==
+
==Pembrolizumab monotherapy {{#subobject:e0d17a|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:60fc19|Variant=1}}===
+
===Regimen {{#subobject:7b36e9|Variant=1}}===
 
{| class="wikitable" style="color:white; background-color:#404040"
 
{| class="wikitable" style="color:white; background-color:#404040"
 
|<small>'''FDA-recommended dose'''</small>
 
|<small>'''FDA-recommended dose'''</small>
Line 387: Line 355:
 
{| class="wikitable" style="width: 60%; text-align:center;"  
 
{| class="wikitable" style="width: 60%; text-align:center;"  
 
!style="width: 33%"|Study
 
!style="width: 33%"|Study
 +
!style="width: 33%"|Years of enrollment
 
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
 
|-
 
|-
−
|[https://doi.org/10.1056/NEJMoa1804980 Schuster et al. 2018 (JULIET)]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881098/ Armand et al. 2016 (KEYNOTE-013)]
−
|style="background-color:#91cf61"|Phase 2
+
|2014-2016
−
| style="background-color:#9ebcda" |ORR: 59% (95% CI, 44-72)
+
|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)
 
|-
 
|-
 
|}
 
|}
−
''The range given is the FDA-recommended dose.''
 
−
<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">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Immunotherapy====
 
====Immunotherapy====
−
*[[Tisagenlecleucel (Kymriah)]] 0.6 to 6 x 10<sup>8</sup> CTL019 transduced viable T-cells IV once on day 0
+
*[[Pembrolizumab (Keytruda)]] 200 mg IV over 30 minutes once on day 1
−
'''One course'''
+
'''21-day cycle for up to 35 cycles (2 years)'''
−
</div></div>
 
−
===References===
 
−
<!-- # '''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]
 
−
=Consolidation after salvage therapy=
 
−
==BFR, then allo HSCT {{#subobject:c2659b|Regimen=1}}==
 
−
BFR: '''<u>B</u>'''endamustine, '''<u>F</u>'''ludarabine, '''<u>R</u>'''ituximab
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:41fd04|Variant=1}}===
 
−
{| class="wikitable" style="width: 40%; text-align:center;"
 
−
!style="width: 25%"|Study
 
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260365/ Khouri et al. 2014 (MDACC 2008-0246)]
 
−
| style="background-color:#ffffbe" |Phase 2, <20 pts in this subgroup
 
−
|-
 
−
|}
 
−
{{#lst:Allogeneic HSCT|41fd04}}
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''MDACC 2008-0246:''' Khouri IF, Wei W, Korbling M, Turturro F, Ahmed S, Alousi A, Anderlini P, Ciurea S, Jabbour E, Oran B, Popat UR, Rondon G, Bassett RL Jr, Gulbis A. BFR (bendamustine, fludarabine, and rituximab) allogeneic conditioning for chronic lymphocytic leukemia/lymphoma: reduced myelosuppression and GVHD. Blood. 2014 Oct 2;124(14):2306-12. Epub 2014 Aug 21. [http://www.bloodjournal.org/content/124/14/2306.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260365/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25145344 PubMed] NCT00880815
+
<!-- # '''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] -->
−
[[Category:Transformed lymphoma regimens]]
+
# '''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:Disease-specific pages]]
 
[[Category:Aggressive lymphomas]]
 
[[Category:Aggressive lymphomas]]
 
[[Category:Non-Hodgkin lymphomas]]
 
[[Category:Non-Hodgkin lymphomas]]

Revision as of 12:12, 29 October 2022

Back to Top

Section editor transclusions

0 regimens on this page
0 variants on this page


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

ESMO

Older

NCCN

Untreated

DA-R-EPOCH

DA-R-EPOCH: Dose Adjusted Rituximab, Etoposide, Prednisone, Oncovin (Vincristine), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin)

Regimen

Study Years of enrollment Evidence
Dunleavy et al. 2013 (NCI 93-C-0133) 1999-2012 Phase 2
Purroy et al. 2014 2002-2008 Phase 2, <20 pts in this subgroup

Targeted therapy

Chemotherapy

  • Etoposide (Vepesid) 50 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 200 mg/m2)
  • Vincristine (Oncovin) 0.4 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1.6 mg/m2; dose was not capped)
  • Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 2 hours once on day 5
  • Doxorubicin (Adriamycin) 10 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m2)

Glucocorticoid therapy

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.

References

  1. 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. link to original article link to supplementary appendix link to PMC article contains dosing details in manuscript PubMed NCT00001337
  2. 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. link to original article PubMed EudraCT 2004-001684-22

R-CHOP

R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
R-CHOP-21
CHOP-R

Example orders

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Pfreundschuh et al. 2006 (NCIC-CTG LY.9) 2000-2003 Phase 3 (E-esc) 1. CHOP
2. CHOEP
3. MACOP-B
4. PMitCEBO 		Seems to have superior EFS

Targeted therapy

Chemotherapy

Glucocorticoid therapy

Supportive therapy

21-day cycle for 6 cycles

Subsequent treatment

References

  1. 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. link to original article contains dosing details in manuscript PubMed
    1. 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. link to original article PubMed

R-CHOP (Prednisolone)

R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisolone

Example orders

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Cunningham et al. 2013 (UK NCRI R-CHOP14v21) 2005-2008 Phase 3 (C) R-CHOP-14 Might have inferior OS1

1Reported efficacy is based on a post-hoc subgroup analysis.

Targeted therapy

Chemotherapy

Glucocorticoid therapy

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

21-day cycle for 8 cycles

References

  1. 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. link to original article contains dosing details in manuscript PubMed ISRCTN16017947
    1. 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. link to original article PubMed

R-CHOP-14 (Prednisolone)

R-CHOP-14: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisolone every 14 days

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Cunningham et al. 2013 (UK NCRI R-CHOP14v21) 2005-2008 Phase 3 (E-esc) R-CHOP-21 Might have superior OS1

1Reported efficacy is based on the 2016 subgroup analysis.

Targeted therapy

Chemotherapy

Glucocorticoid therapy

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

14-day cycle for 6 cycles (8 cycles of rituximab)

References

  1. 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. link to original article contains dosing details in manuscript PubMed ISRCTN16017947
    1. 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. link to original article PubMed

Consolidation after upfront therapy

Radiation therapy

Regimen

Study Evidence
Pfreundschuh et al. 2006 (NCIC-CTG LY.9) Non-randomized portion of RCT

Preceding treatment

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

References

  1. 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. link to original article contains dosing details in manuscript PubMed NCT00064116
    1. 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. link to original article PubMed

Relapsed or refractory, salvage therapy

R-DHAP

R-DHAP: Rituximab, Dexamethasone, High-dose Ara-C (Cytarabine), Platinol (Cisplatin)

Regimen

Study Evidence Comparator
Crump et al. 2014 (NCIC-CTG LY.12) Phase 3, <20 pts in subgroup (C) R-GDP

Targeted therapy

Glucocorticoid therapy

Chemotherapy

  • Cytarabine (Ara-C) 2000 mg/m2 IV over 3 hours every 12 hours on day 2 (total dose per cycle: 4000 mg/m2)
  • Cisplatin (Platinol) 100 mg/m2 IV continuous infusion over 24 hours, started on day 1

21-day cycle for up to 3 cycles

References

  1. 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. link to original article contains dosing details in manuscript PubMed NCT00078949

R-GDP

R-GDP: Rituximab, Gemcitabine, Dexamethasone, Platinol (Cisplatin)

Regimen

Study Evidence Comparator
Crump et al. 2014 (NCIC-CTG LY.12) Phase 3, <20 pts in subgroup (E-switch-ic) R-DHAP

Targeted therapy

Chemotherapy

Glucocorticoid therapy

21-day cycle for up to 3 cycles

References

  1. 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. link to original article contains dosing details in manuscript PubMed NCT00078949

Consolidation after salvage therapy

FluBuCy, then allo HSCT

FluBuCy: Fludarabine, Busulfan, Cyclophosphamide

Regimen

Study Evidence
Glass et al. 2014 (DSHNHL R3) Phase 2

Chemotherapy

Immunotherapy

GVHD prophylaxis

One course

References

  1. 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. link to original article link to original protocol (in German) contains dosing details in manuscript PubMed NCT00785330

Relapsed or refractory, further lines of therapy

Axicabtagene ciloleucel monotherapy

Regimen

FDA-recommended dose
Study Years of enrollment Evidence Efficacy
Locke et al. 2017 (ZUMA-1) 2015-2016 Phase 1/2, <20 pts in subgroup (RT) ORR: 82%

Preceding treatment

  • Lymphodepletion with FC

Immunotherapy

Supportive therapy

One course; patients with initial response and disease progression at least 3 months later could be retreated

References

  1. 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. link to original article link to PMC article PubMed NCT02348216
    1. 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. link to original article contains dosing details in manuscript link to PMC article PubMed
    2. 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. link to original article link to PMC article contains dosing details in manuscript PubMed

Lisocabtagene maraleucel monotherapy

Regimen

Study Years of enrollment Evidence
Abramson et al. 2020 (TRANSCEND NHL-001) 2016-2019 Phase 1 (RT)

Immunotherapy

References

  1. 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. link to original article PubMed NCT02631044

Pembrolizumab monotherapy

Regimen

FDA-recommended dose
Study Years of enrollment Evidence
Armand et al. 2016 (KEYNOTE-013) 2014-2016 Phase 1b
Armand et al. 2016 (KEYNOTE-170) 2016-2017 Phase 2 (RT)

Immunotherapy

21-day cycle for up to 35 cycles (2 years)

References

  1. 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. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01953692
  2. 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. link to original article contains dosing details in manuscript link to PMC article PubMed NCT02576990
Retrieved from "https://hemonc.org/w/index.php?title=Staging_page&oldid=63626"