Difference between revisions of "Primary mediastinal B-cell lymphoma"

From HemOnc.org - A Hematology Oncology Wiki
Jump to navigation Jump to search
m
(97 intermediate revisions by 3 users not shown)
Line 1: Line 1:
{| class="wikitable" style="text-align:center; width:50%;"
+
<span id="BackToTop"></span>
!colspan="2" align="center" style="color:white; font-size:125%; background-color:#de2d26"|'''Section editor'''
+
<div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px">
|-
+
[[#top|Back to Top]]
|style="background-color:#F0F0F0"|[[File:Jcvillasboas.jpg|frameless|upright=0.3|center]]
+
</div>
|<big>[[User:Jcvillasboas|J.C. Villasboas Bisneto, MD]]<br>Mayo Clinic<br>Rochester, MN</big>
+
{{#lst:Editorial board transclusions|anhl}}
|-
 
|}
 
 
{| class="wikitable" style="float:right; margin-right: 5px;"
 
{| class="wikitable" style="float:right; margin-right: 5px;"
 
|-
 
|-
Line 14: Line 12:
 
''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.''
 
''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=
 
=Guidelines=
 +
'''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.'''
 
==BSH==
 
==BSH==
*'''2019:''' Cwynarski et al. [https://onlinelibrary.wiley.com/doi/10.1111/bjh.15731 The management of primary mediastinal B-cell lymphoma: a British Society for Haematology Good Practice Paper]
+
*'''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] [https://www.ncbi.nlm.nih.gov/pubmed/30609016 PubMed]
 +
==[https://www.esmo.org/ ESMO]==
 +
*'''2016:''' Vitolo et al. [https://doi.org/10.1093/annonc/mdw175 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]
  
==[http://www.esmo.org/ ESMO]==
+
*'''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]
*'''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://www.ncbi.nlm.nih.gov/pubmed/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://www.ncbi.nlm.nih.gov/pubmed/23175624 PubMed]
 
  
==[https://www.nccn.org/ NCCN]==
+
==NCCN==
*[https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf NCCN Guidelines - B-cell Lymphomas]
+
*''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1480 NCCN Guidelines - B-cell Lymphomas].''
  
 
=Untreated=
 
=Untreated=
 
 
==DA-R-EPOCH {{#subobject:d7244e|Regimen=1}}==
 
==DA-R-EPOCH {{#subobject:d7244e|Regimen=1}}==
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
 
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)
 
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}}===
 
===Regimen {{#subobject:98dcb9|Variant=1}}===
{| class="wikitable" style="width: 50%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
!style="width: 25%"|Study
+
!style="width: 33%"|Study
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
|[https://www.nejm.org/doi/full/10.1056/NEJMoa1214561 Dunleavy et al. 2013 (NCI 93-C-0133)]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4568999/ Dunleavy et al. 2013 (NCI 93-C-0133<sub>PMBCL</sub>)]
|style="background-color:#91cf61"|Phase II
+
|1999-2012
 +
|style="background-color:#91cf61"|Phase 2
 
|-
 
|-
|[https://onlinelibrary.wiley.com/doi/10.1111/bjh.13273/full Purroy et al. 2014]
+
|[https://doi.org/10.1111/bjh.13273 Purroy et al. 2014]
|style="background-color:#ffffbe"|Phase II, <20 pts in this subgroup
+
|2002-2008
 +
|style="background-color:#ffffbe"|Phase 2, fewer than 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====
 
====Chemotherapy====
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV over 3 hours once on day 1
 
 
*[[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>)  
 
*[[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>)  
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO twice per day on days 1 to 5
 
 
*[[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)  
 
*[[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
 
*[[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>)
 
*[[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====
====Supportive medications====
+
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO twice per day on days 1 to 5
*[[Filgrastim (Neupogen)]] 300 mcg SC once per day, starting on day 6 and continuing until ANC greater than 5,000/uL past nadir
+
====Supportive therapy====
 +
*[[Filgrastim (Neupogen)]] 300 mcg SC once per day, starting on day 6 and continuing until ANC greater than 5,000/μL past nadir
 
*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] 160/800 mg (or equivalent if allergic) PO once per day on 3 days per week
 
*[[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)"
 
**Note: It's assumed this is what the supplement for Dunleavy et al. 2013 meant by "Baxtrim (sulphametoxazole and trimethoprim)"
Line 62: Line 60:
 
*Lactulose 20 g PO every 6 hours 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
 
*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'''
 
'''21-day cycle for 6 to 8 cycles'''
 
+
</div>
====Dose adjustments====
+
<div class="toccolours" style="background-color:#fff2ae">
 +
====Dose and schedule modifications====
 
*Start cycle 1 as described above.
 
*Start cycle 1 as described above.
 
*Obtain CBCs twice per week for nadir measurements.
 
*Obtain CBCs twice per week for nadir measurements.
Line 71: Line 69:
 
*If nadir ANC less than 500, use same doses as last 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.
 
*If nadir platelet count less than 25,000, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to the previous cycle.
 
+
</div></div>
 
===References===
 
===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://www.nejm.org/doi/full/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] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23574119 PubMed]
+
# '''NCI 93-C-0133<sub>PMBCL</sub>:''' 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] [https://clinicaltrials.gov/study/NCT00001337 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://onlinelibrary.wiley.com/doi/10.1111/bjh.13273/full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25521006 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
 
 
 
==R-CHOP {{#subobject:796753|Regimen=1}}==
 
==R-CHOP {{#subobject:796753|Regimen=1}}==
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
 
R-CHOP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone
 
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>R-CHOP-21
Line 86: Line 79:
 
===Example orders===
 
===Example orders===
 
*[[Example orders for R-CHOP in lymphoma]]
 
*[[Example orders for R-CHOP in lymphoma]]
 
+
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:283715|Variant=1}}===
 
===Regimen {{#subobject:283715|Variant=1}}===
{| class="wikitable" style="width: 100%; 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%"|Dates of enrollment
!style="width: 25%"|Comparator
+
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2806%2970664-7/fulltext Pfreundschuh et al. 2006 (NCIC CTG LY.9)]
+
|[https://doi.org/10.1016/S1470-2045%2806%2970664-7 Pfreundschuh et al. 2006 (NCIC-CTG LY.9)]
|style="background-color:#1a9851"|Phase III (E-esc)
+
|2000-2003
|1. CHOP<br> 2. CHOEP<br> 3. MACOP-B<br> 4. PMitCEBO
+
|style="background-color:#1a9851"|Phase 3 (E-esc)
|style="background-color:#91cf60"|Seems to have superior EFS
+
|1a. [[#CHOP_888|CHOP]]<br>1b. [[#CHOEP-21_888|CHOEP-21]]<br>1c. [[#MACOP-B_888|MACOP-B]]<br>1d. [[#PMitCEBO_888|PMitCEBO]]
 +
|style="background-color:#91cf60"|Seems to have superior EFS (primary endpoint)<br>EFS36: 79% vs 59%
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
====Chemotherapy====
 
====Chemotherapy====
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
 
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
*[[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
 
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
*[[Vincristine (Oncovin)]] 2 mg 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
 
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
+
====Supportive therapy====
====Supportive medications====
 
 
*G-CSF with one of the following:
 
*G-CSF with one of the following:
 
**[[Filgrastim (Neupogen)]] used at physician discretion for neutropenia
 
**[[Filgrastim (Neupogen)]] used at physician discretion for neutropenia
 
**[[Lenograstim (Granocyte)]] used at physician discretion for neutropenia
 
**[[Lenograstim (Granocyte)]] used at physician discretion for neutropenia
 
 
'''21-day cycle for 6 cycles'''
 
'''21-day cycle for 6 cycles'''
 
+
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 
====Subsequent treatment====
 
====Subsequent treatment====
*[[#Radiation_therapy|Radiation therapy]]
+
*[[#Radiation_therapy|RT]] consolidation
 +
</div></div>
  
 
===References===
 
===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://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2806%2970664-7/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16648042 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]
## '''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. [http://annonc.oxfordjournals.org/content/22/3/664.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20724576 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 (Prednisolone) {{#subobject:7a9c53|Regimen=1}}==
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
 
R-CHOP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisolone
 
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===
 
*[[Example orders for R-CHOP in lymphoma]]
 
*[[Example orders for R-CHOP in lymphoma]]
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:74f424|Variant=1}}===
 
===Regimen {{#subobject:74f424|Variant=1}}===
{| class="wikitable" style="width: 100%; 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%"|Dates of enrollment
!style="width: 25%"|Comparator
+
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)60313-X/fulltext Cunningham et al. 2013 (UK NCRI R-CHOP14v21)]
+
|[https://doi.org/10.1016/S0140-6736(13)60313-X Cunningham et al. 2013 (UK NCRI R-CHOP14v21)]
|style="background-color:#1a9851"|Phase III (C)
+
|2005-2008
 +
|style="background-color:#1a9851"|Phase 3 (C)
 
|[[#R-CHOP-14_.28Prednisolone.29|R-CHOP-14]]
 
|[[#R-CHOP-14_.28Prednisolone.29|R-CHOP-14]]
| style="background-color:#fee08b" |Might have inferior OS (*)
+
| style="background-color:#fee08b" |Might have inferior OS<sup>1</sup>
 
|-
 
|-
 
|}
 
|}
''Note: the efficacy reported here is based on a post-hoc subgroup analysis.''
+
''<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====
 
====Chemotherapy====
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
 
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
*[[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
 
*[[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
 
*[[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
 
*[[Prednisolone (Millipred)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
 
+
====CNS therapy, prophylaxis====
====CNS 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:
 
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.
 
*[[Methotrexate (MTX)]] 12.5 mg IT "for the first three cycles of treatment, administered as per local guidelines." No other details given.
 
+
====Supportive therapy====
====Supportive medications====
 
 
*[[Lenograstim (Granocyte)]] (dose/route not specified) given on days 4 to 12 at physician discretion
 
*[[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
 
*[[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
 
*[[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'''
 
'''21-day cycle for 8 cycles'''
 
+
</div></div>
 
===References===
 
===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://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)60313-X/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23615461 PubMed]
+
# '''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/full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27477167 PubMed]
+
## '''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 (Prednisolone) {{#subobject:fc3bde|Regimen=1}}==
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
 
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
 
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}}===
 
===Regimen {{#subobject:8136b1|Variant=1}}===
{| class="wikitable" style="width: 100%; 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%"|Dates of enrollment
!style="width: 25%"|Comparator
+
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)60313-X/fulltext Cunningham et al. 2013 (UK NCRI R-CHOP14v21)]
+
|[https://doi.org/10.1016/S0140-6736(13)60313-X Cunningham et al. 2013 (UK NCRI R-CHOP14v21)]
|style="background-color:#1a9851"|Phase III (E-esc)
+
|2005-2008
 +
|style="background-color:#1a9851"|Phase 3 (E-esc)
 
|[[#R-CHOP|R-CHOP-21]]
 
|[[#R-CHOP|R-CHOP-21]]
| style="background-color:#d9ef8b" |Might have superior OS (*)
+
| style="background-color:#d9ef8b" |Might have superior OS<sup>1</sup> (primary endpoint)
 
|-
 
|-
 
|}
 
|}
''Note: the efficacy reported here is based on a post-hoc subgroup analysis.''
+
''<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====
 
====Chemotherapy====
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
 
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
 
*[[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
 
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
*[[Vincristine (Oncovin)]] 2 mg 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
 
*[[Prednisolone (Millipred)]] 100 mg PO once per day on days 1 to 5
 
+
====CNS therapy, prophylaxis====
====CNS 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:
 
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.
 
*[[Methotrexate (MTX)]] 12.5 mg IT "for the first three cycles of treatment, administered as per local guidelines." No other details given.
 
+
====Supportive therapy====
====Supportive medications====
 
 
*[[Lenograstim (Granocyte)]] (dose/route not specified) given on days 4 to 12
 
*[[Lenograstim (Granocyte)]] (dose/route not specified) given on days 4 to 12
 
*[[Allopurinol (Zyloprim)]] 300 mg PO once per day during cycle 1
 
*[[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
 
*[[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)'''
 
'''14-day cycle for 6 cycles (8 cycles of rituximab)'''
 +
</div></div>
 
===References===
 
===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://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)60313-X/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23615461 PubMed]
+
# '''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/full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27477167 PubMed]
+
## '''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=
 
=Consolidation after upfront therapy=
 
==Radiation therapy {{#subobject:89ce8b|Regimen=1}}==
 
==Radiation therapy {{#subobject:89ce8b|Regimen=1}}==
{| class="wikitable" style="float:right; margin-left: 5px;"
+
<div class="toccolours" style="background-color:#eeeeee">
|-
 
|[[#top|back to top]]
 
|}
 
 
===Regimen {{#subobject:952fa4|Variant=1}}===
 
===Regimen {{#subobject:952fa4|Variant=1}}===
{| class="wikitable" style="width: 50%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
!style="width: 25%"|Study
+
!style="width: 33%"|Study
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2806%2970664-7/fulltext Pfreundschuh et al. 2006 (NCIC CTG LY.9)]
+
|[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
+
|2000-2003
 +
| style="background-color:#91cf61" |Non-randomized part of phase 3 RCT
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#cbd5e8">
 
====Preceding treatment====
 
====Preceding treatment====
*CHOP-like therapy x 6 versus R-CHOP-like therapy (including [[#R-CHOP|R-CHOP]]x 6
+
*Induction [[#CHOP|CHOP]] x 6 or [[#CHOEP_888|CHOEP]] 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====
 
====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
+
*[[External beam radiotherapy]]: 30 to 4000 cGy given to sites of primary bulky disease; 30 to 4000 cGy to primary extranodal disease at physician discretion
 
+
</div></div>
 
===References===
 
===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://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2806%2970664-7/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16648042 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] [https://clinicaltrials.gov/study/NCT00064116 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. [http://annonc.oxfordjournals.org/content/22/3/664.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20724576 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]
 
 
 
=Relapsed or refractory, salvage therapy=
 
=Relapsed or refractory, salvage therapy=
 
 
==R-DHAP {{#subobject:26123c|Regimen=1}}==
 
==R-DHAP {{#subobject:26123c|Regimen=1}}==
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
 
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">
 
===Regimen {{#subobject:2ed78f|Variant=1}}===
 
===Regimen {{#subobject:2ed78f|Variant=1}}===
{| class="wikitable" style="width: 100%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
!Study
 
!Study
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
![[Levels_of_Evidence#Evidence|Evidence]]
 
!Comparator
 
!Comparator
 
|-
 
|-
|[http://jco.ascopubs.org/content/32/31/3490.full 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)]
|style="background-color:#91cf61"|Phase III, <20 pts in subgroup (C)
+
|style="background-color:#91cf61"|Phase 3, fewer than 20 pts in subgroup (C)
 
|[[Primary_mediastinal_B-cell_lymphoma#R-GDP|R-GDP]]
 
|[[Primary_mediastinal_B-cell_lymphoma#R-GDP|R-GDP]]
 
|-
 
|-
 
|}
 
|}
====Chemotherapy====
+
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
*[[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
 
*[[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>)
 
*[[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
 
*[[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'''
 
'''21-day cycle for up to 3 cycles'''
 
+
</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. -->
# 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. [http://jco.ascopubs.org/content/32/31/3490.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25267740 PubMed]
+
# '''NCIC-CTG LY.12:''' Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. Epub 2014 Sep 29. [https://doi.org/10.1200/jco.2013.53.9593 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25267740/ PubMed] [https://clinicaltrials.gov/study/NCT00078949 NCT00078949]
 
 
 
==R-GDP {{#subobject:f6075a|Regimen=1}}==
 
==R-GDP {{#subobject:f6075a|Regimen=1}}==
{| class="wikitable" style="float:right; margin-left: 5px;"
 
|-
 
|[[#top|back to top]]
 
|}
 
 
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">
 
===Regimen {{#subobject:8091c0|Variant=1}}===
 
===Regimen {{#subobject:8091c0|Variant=1}}===
{| class="wikitable" style="width: 100%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
!Study
+
!style="width: 20%"|Study
![[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 20%"|Dates of enrollment
!Comparator
+
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
|[http://jco.ascopubs.org/content/32/31/3490.full 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)]
|style="background-color:#91cf61"|Phase III, <20 pts in subgroup (E-switch-ic)
+
|2003-2011
 +
|style="background-color:#91cf61"|Phase 3, fewer than 20 pts in subgroup (E-switch-ic)
 
|[[Primary_mediastinal_B-cell_lymphoma#R-DHAP|R-DHAP]]
 
|[[Primary_mediastinal_B-cell_lymphoma#R-DHAP|R-DHAP]]
 +
| style="background-color:#eeee01" |Non-inferior RR after 2 cycles (primary endpoint)
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
====Chemotherapy====
 
====Chemotherapy====
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
 
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
*[[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
 
*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
 
 
 
'''21-day cycle for up to 3 cycles'''
 
'''21-day cycle for up to 3 cycles'''
 
+
</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. [http://jco.ascopubs.org/content/32/31/3490.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25267740 PubMed]
+
# '''NCIC-CTG LY.12:''' Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol. 2014 Nov 1;32(31):3490-6. Epub 2014 Sep 29. [https://doi.org/10.1200/jco.2013.53.9593 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25267740/ PubMed] [https://clinicaltrials.gov/study/NCT00078949 NCT00078949]
 
 
 
=Consolidation after salvage therapy=
 
=Consolidation after salvage therapy=
==FluBuCy, then allo HSCT {{#subobject:84acb0|Regimen=1}}==
+
==Fludarabine, Busulfan, Cyclophosphamide, then allo HSCT {{#subobject:84acb0|Regimen=1}}==
{| class="wikitable" style="float:right; margin-left: 5px;"
+
FluBuCy: '''<u>Flu</u>'''darabine, '''<u>Bu</u>'''sulfan, '''<u>Cy</u>'''clophosphamide
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, oral {{#subobject:bfe434|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://doi.org/10.1016/S1470-2045(14)70161-5 Glass et al. 2014 (DSHNHL R3)]
 +
|2004-06-16 to 2009-03-24
 +
| style="background-color:#91cf61" |Phase 2
 
|-
 
|-
|[[#top|back to top]]
 
 
|}
 
|}
FluBuCy: '''<u>Flu</u>'''darabine, '''<u>Bu</u>'''sulfan, '''<u>Cy</u>'''clophosphamide
+
{{#lst:Allogeneic HSCT|bfe434}}
===Regimen {{#subobject:bfe434|Variant=1}}===
+
</div></div><br>
{| class="wikitable" style="width: 50%; text-align:center;"  
+
<div class="toccolours" style="background-color:#eeeeee">
!style="width: 25%"|Study
+
===Regimen variant #2, intravenous {{#subobject:bfe434|Variant=1}}===
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70161-5/fulltext Glass et al. 2014 (DSHNHL R3)]
+
|[https://doi.org/10.1016/S1470-2045(14)70161-5 Glass et al. 2014 (DSHNHL R3)]
| style="background-color:#91cf61" |Phase II
+
|2004-06-16 to 2009-03-24
 +
| style="background-color:#91cf61" |Phase 2
 
|-
 
|-
 
|}
 
|}
{{#lst:Allogeneic HSCT|bfe434}}
+
{{#lst:Allogeneic HSCT|bfe435}}
====Immunotherapy====
+
</div></div>
*[[Allogeneic stem cells]]
 
'''Stem cells transfused on day 0'''
 
 
===References===
 
===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) -->
 
<!-- # 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://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70161-5/fulltext link to original article] [http://www.dshnhl.org/app/download/9495510598/Studienprotokoll+DSHNHL+alloFBC+final+vollst.pdf link to original protocol (in German)] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24827808 PubMed]
+
# '''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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24827808/ PubMed] [https://clinicaltrials.gov/study/NCT00785330 NCT00785330]
  
 
=Relapsed or refractory, further lines of therapy=
 
=Relapsed or refractory, further lines of therapy=
 
==Axicabtagene ciloleucel monotherapy {{#subobject:78231d|Regimen=1}}==
 
==Axicabtagene ciloleucel monotherapy {{#subobject:78231d|Regimen=1}}==
{| class="wikitable" style="float:right; margin-left: 5px;"
+
<div class="toccolours" style="background-color:#eeeeee">
|-
 
|[[#top|back to top]]
 
|}
 
 
===Regimen {{#subobject:e3e516|Variant=1}}===
 
===Regimen {{#subobject:e3e516|Variant=1}}===
 
{| class="wikitable" style="color:white; background-color:#404040"
 
{| class="wikitable" style="color:white; background-color:#404040"
Line 326: Line 328:
 
|-
 
|-
 
|}
 
|}
{| class="wikitable" style="width: 100%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 80%; text-align:center;"  
 
!style="width: 25%"|Study
 
!style="width: 25%"|Study
!style="width: 25%"|Years of enrollment
+
!style="width: 25%"|Dates 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]]
 
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|-
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882485/ Nellapu et al. 2017 (ZUMA-1)]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363293/ Locke et al. 2017 (ZUMA-1)]
 
|2015-2016
 
|2015-2016
|style="background-color:#ffffbe"|Phase II, <20 pts in subgroup (RT)
+
|style="background-color:#ffffbe"|Phase 1/2, fewer than 20 pts in subgroup (RT)
 
| style="background-color:#e0ecf4" |ORR: 82%
 
| style="background-color:#e0ecf4" |ORR: 82%
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#cbd5e8">
 
====Preceding treatment====
 
====Preceding treatment====
*Lymphodepletion with [[Autologous_HSCT#FC|FC]]
+
*Lymphodepletion with [[Autologous_HSCT#Cyclophosphamide_.26_Fludarabine_.28FC.29|FC]]
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Immunotherapy====
 
====Immunotherapy====
*[[Axicabtagene ciloleucel (Yescarta)]] target dose of 2 × 10<sup>6</sup> CAR T cells/kg IV once on day 0
+
*[[Axicabtagene ciloleucel (Yescarta)]] target dose of 2 x 10<sup>6</sup> CAR T cells/kg IV once on day 0
 
+
====Supportive therapy====
====Supportive medications====
+
*[[Acetaminophen (Tylenol)]] 650 mg PO once on day 0, approximately 60 minutes prior to axi-cel
*[[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 axi-cel
*[[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'''
 
'''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] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28129122/ PubMed] [https://clinicaltrials.gov/study/NCT02348216 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]
 +
##'''Update:''' Neelapu SS, Jacobson CA, Ghobadi A, 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 AH, McSweeney PA, Munoz J, Siddiqi T, Chavez JC, Herrera AF, Bartlett NL, Bot AA, Shen RR, Dong J, Singh K, Miao H, Kim JJ, Zheng Y, Locke FL. Five-year follow-up of ZUMA-1 supports the curative potential of axicabtagene ciloleucel in refractory large B-cell lymphoma. Blood. 2023 May 11;141(19):2307-2315. [https://doi.org/10.1182/blood.2022018893 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36821768/ 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%"|Dates 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)]
 +
|2016-01-11 to 2019-07-05
 +
| style="background-color:#91cf61" |Phase 1 (RT)
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Immunotherapy====
 +
*[[Lisocabtagene maraleucel (Breyanzi)]] target dose of 100 x 10<sup>6</sup> CAR T cells IV once on day 0
 +
'''One course'''
 +
</div></div>
 
===References===
 
===References===
# '''ZUMA-1:''' 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://www.nejm.org/doi/full/10.1056/NEJMoa1707447 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882485/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29226797 PubMed]
+
#'''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] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/32888407/ PubMed] [https://clinicaltrials.gov/study/NCT02631044 NCT02631044]
 +
##'''Update:''' Abramson JS, Palomba ML, Gordon LI, Lunning M, Wang M, Arnason J, Purev E, Maloney DG, Andreadis C, Sehgal A, Solomon SR, Ghosh N, Dehner C, Kim Y, Ogasawara K, Kostic A, Siddiqi T. Two-year follow-up of lisocabtagene maraleucel in relapsed or refractory large B-cell lymphoma in TRANSCEND NHL 001. Blood. 2024 Feb 1;143(5):404-416. [https://doi.org/10.1182/blood.2023020854 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37890149/ PubMed]
  
 
==Pembrolizumab monotherapy {{#subobject:e0d17a|Regimen=1}}==
 
==Pembrolizumab monotherapy {{#subobject:e0d17a|Regimen=1}}==
{| class="wikitable" style="float:right; margin-left: 5px;"
+
<div class="toccolours" style="background-color:#eeeeee">
|-
 
|[[#top|back to top]]
 
|}
 
 
===Regimen {{#subobject:7b36e9|Variant=1}}===
 
===Regimen {{#subobject:7b36e9|Variant=1}}===
 
{| class="wikitable" style="color:white; background-color:#404040"
 
{| class="wikitable" style="color:white; background-color:#404040"
Line 362: Line 388:
 
|-
 
|-
 
|}
 
|}
{| class="wikitable" style="width: 75%; 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%"|Dates of enrollment
 
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881098/ Armand et al. 2016 (KEYNOTE-013)]
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881098/ Armand et al. 2016 (KEYNOTE-013)]
 
|2014-2016
 
|2014-2016
|style="background-color:#91cf61"|Phase Ib
+
|style="background-color:#91cf61"|Phase 1b
 
|-
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881098/ Armand et al. 2016 (KEYNOTE-170)]
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881098/ Armand et al. 2016 (KEYNOTE-170)]
 
|2016-2017
 
|2016-2017
|style="background-color:#91cf61"|Phase II (RT)
+
|style="background-color:#91cf61"|Phase 2 (RT)
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Immunotherapy====
 
====Immunotherapy====
 
*[[Pembrolizumab (Keytruda)]] 200 mg IV over 30 minutes once on day 1
 
*[[Pembrolizumab (Keytruda)]] 200 mg IV over 30 minutes once on day 1
 
 
'''21-day cycle for up to 35 cycles (2 years)'''
 
'''21-day cycle for up to 35 cycles (2 years)'''
 
+
</div></div>
 
===References===
 
===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] -->
 
<!-- # '''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] -->
# 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,
+
# '''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] [https://clinicaltrials.gov/study/NCT01953692 NCT01953692]
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://ascopubs.org/doi/full/10.1200/JCO.19.01389 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881098/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/31609651 PubMed]
+
# '''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] [https://clinicaltrials.gov/study/NCT02576990 NCT02576990]
 
+
##'''Update:''' Zinzani PL, Thieblemont C, Melnichenko V, Bouabdallah K, Walewski J, Majlis A, Fogliatto L, Garcia-Sancho AM, Christian B, Gulbas Z, Özcan M, Perini GF, Ghesquieres H, Shipp MA, Thompson S, Chakraborty S, Marinello P, Armand P. Pembrolizumab in relapsed or refractory primary mediastinal large B-cell lymphoma: final analysis of KEYNOTE-170. Blood. 2023 Jul 13;142(2):141-145. [https://doi.org/10.1182/blood.2022019340 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37130017/ PubMed]
 
[[Category:Primary mediastinal B-cell lymphoma regimens]]
 
[[Category:Primary mediastinal B-cell lymphoma regimens]]
 
[[Category:Disease-specific pages]]
 
[[Category:Disease-specific pages]]
[[Category:Aggressive lymphomas]]
+
[[Category:Aggressive non-Hodgkin lymphomas]]
[[Category:Non-Hodgkin lymphomas]]
+
[[Category:B-cell lymphomas]]

Revision as of 19:05, 26 June 2024

Section editor
TarsheenSethi.jpg
Tarsheen Sethi, MD, MSCI
Yale University
New Haven, CT, USA

LinkedIn
11 regimens on this page
11 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

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

BSH

ESMO

NCCN

Untreated

DA-R-EPOCH

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

Regimen

Study Dates of enrollment Evidence
Dunleavy et al. 2013 (NCI 93-C-0133PMBCL) 1999-2012 Phase 2
Purroy et al. 2014 2002-2008 Phase 2, fewer than 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/μL 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 and schedule 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-0133PMBCL: 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 Dates of enrollment Evidence Comparator Comparative Efficacy
Pfreundschuh et al. 2006 (NCIC-CTG LY.9) 2000-2003 Phase 3 (E-esc) 1a. CHOP
1b. CHOEP-21
1c. MACOP-B
1d. PMitCEBO
Seems to have superior EFS (primary endpoint)
EFS36: 79% vs 59%

Targeted therapy

Chemotherapy

Glucocorticoid therapy

Supportive therapy

21-day cycle for 6 cycles

Subsequent treatment

  • RT consolidation

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 Dates 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 Dates 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 (primary endpoint)

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 Dates of enrollment Evidence
Pfreundschuh et al. 2006 (NCIC-CTG LY.9) 2000-2003 Non-randomized part of phase 3 RCT

Preceding treatment

Radiotherapy

  • External beam radiotherapy: 30 to 4000 cGy given to sites of primary bulky disease; 30 to 4000 cGy 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, fewer than 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 Dates of enrollment Evidence Comparator Comparative Efficacy
Crump et al. 2014 (NCIC-CTG LY.12) 2003-2011 Phase 3, fewer than 20 pts in subgroup (E-switch-ic) R-DHAP Non-inferior RR after 2 cycles (primary endpoint)

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

Fludarabine, Busulfan, Cyclophosphamide, then allo HSCT

FluBuCy: Fludarabine, Busulfan, Cyclophosphamide

Regimen variant #1, oral

Study Dates of enrollment Evidence
Glass et al. 2014 (DSHNHL R3) 2004-06-16 to 2009-03-24 Phase 2

Chemotherapy

Immunotherapy

GVHD prophylaxis

One course


Regimen variant #2, intravenous

Study Dates of enrollment Evidence
Glass et al. 2014 (DSHNHL R3) 2004-06-16 to 2009-03-24 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 contains dosing details in manuscript PubMed NCT00785330

Relapsed or refractory, further lines of therapy

Axicabtagene ciloleucel monotherapy

Regimen

FDA-recommended dose
Study Dates of enrollment Evidence Efficacy
Locke et al. 2017 (ZUMA-1) 2015-2016 Phase 1/2, fewer than 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 contains dosing details in manuscript 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
    3. Update: Neelapu SS, Jacobson CA, Ghobadi A, 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 AH, McSweeney PA, Munoz J, Siddiqi T, Chavez JC, Herrera AF, Bartlett NL, Bot AA, Shen RR, Dong J, Singh K, Miao H, Kim JJ, Zheng Y, Locke FL. Five-year follow-up of ZUMA-1 supports the curative potential of axicabtagene ciloleucel in refractory large B-cell lymphoma. Blood. 2023 May 11;141(19):2307-2315. link to original article PubMed

Lisocabtagene maraleucel monotherapy

Regimen

Study Dates of enrollment Evidence
Abramson et al. 2020 (TRANSCEND NHL-001) 2016-01-11 to 2019-07-05 Phase 1 (RT)

Immunotherapy

One course

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 contains dosing details in abstract PubMed NCT02631044
    1. Update: Abramson JS, Palomba ML, Gordon LI, Lunning M, Wang M, Arnason J, Purev E, Maloney DG, Andreadis C, Sehgal A, Solomon SR, Ghosh N, Dehner C, Kim Y, Ogasawara K, Kostic A, Siddiqi T. Two-year follow-up of lisocabtagene maraleucel in relapsed or refractory large B-cell lymphoma in TRANSCEND NHL 001. Blood. 2024 Feb 1;143(5):404-416. link to original article PubMed

Pembrolizumab monotherapy

Regimen

FDA-recommended dose
Study Dates 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
    1. Update: Zinzani PL, Thieblemont C, Melnichenko V, Bouabdallah K, Walewski J, Majlis A, Fogliatto L, Garcia-Sancho AM, Christian B, Gulbas Z, Özcan M, Perini GF, Ghesquieres H, Shipp MA, Thompson S, Chakraborty S, Marinello P, Armand P. Pembrolizumab in relapsed or refractory primary mediastinal large B-cell lymphoma: final analysis of KEYNOTE-170. Blood. 2023 Jul 13;142(2):141-145. link to original article PubMed