Transformed lymphoma

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Last updated on 2024-07-23:18 regimens on this page
18 variants on this page
Transformed lymphoma, often referred to as Richter's transformation, most commonly arises from a preceding indolent lymphoma - usually follicular lymphoma or chronic lymphocytic leukemia. It is typically treated as per the histologic subtype, which is usually DLBCL. However, some regimens specific to transformed lymphoma have been developed and are included here.
=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.
==NCCN==
*NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - B-cell Lymphomas and NCCN Guidelines - Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.
=All lines of therapy=
==Axicabtagene ciloleucel monotherapy==
===Regimen===
FDA-recommended dose
Study 	Dates of enrollment	Evidence 	Efficacy
Locke et al. 2017 (ZUMA-1)	2015-11 to 2016-09 	Phase 1/2, fewer than 20 pts in subgroup (RT)	ORR: 82%, 95% CI 72-89
====Preceding treatment====
*Lymphodepletion with FC
====Immunotherapy====
*Axicabtagene ciloleucel (Yescarta) target dose of 2 x 106 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 axi-cel
*Diphenhydramine (Benadryl) 12.5 mg IV or PO once on day 0, approximately 60 minutes prior to axi-cel
 
One course; patients with initial response and disease progression at least 3 months later could be retreated
===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. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC 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. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
##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 dosing details in manuscript have been reviewed by our editors EuroPMC
##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 link to PMC article EuroPMC
==Bendamustine monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Friedberg et al. 2008	2003-09 to 2005-02 	Phase 2, fewer than 20 pts in this subgroup
====Chemotherapy====
*Bendamustine 120 mg/m2 IV once per day on days 1 & 2
21-day cycle for up to 12 cycles
===References===
# 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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Epcoritamab monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence
Hutchings et al. 2021 (EPCORE NHL-1)	2020-06-19 to 2022-01-31	Phase 1/2 (RT)
Note: dates of enrollment are based on the dose-expansion cohort.
====Immunotherapy====
*Epcoritamab (Epkinly) as follows:
**Cycle 1: 0.16 mg SC once on day 1, then 0.8 mg SC once on day 8, then 48 mg SC once per day on days 15 & 22
**Cycles 2 & 3: 48 mg SC once per day on days 1, 8, 15, 22
**Cycles 4 to 9: 48 mg SC once per day on days 1 & 15
**Cycle 10 onwards: 48 mg SC once on day 1
====Supportive therapy====
*Prednisolone (Millipred) as follows:
**Cycle 1: 100 mg PO or IV once per day on days 1 to 4, 8 to 11, 15 to 18, 22 to 25, given 30 to 120 minutes prior to epcoritamab on treatment days 1, 8, 15, 22
*Diphenhydramine (Benadryl) as follows:
**Cycle 1: 50 mg PO or IV once per day on days 1, 8, 15, 22
*Acetaminophen (Tylenol) as follows:
**Cycle 1: 650 to 1000 mg PO once per day on days 1, 8, 15, 22
28-day cycles
===References===
#EPCORE NHL-1: Hutchings M, Mous R, Clausen MR, Johnson P, Linton KM, Chamuleau MED, Lewis DJ, Sureda Balari A, Cunningham D, Oliveri RS, Elliott B, DeMarco D, Azaryan A, Chiu C, Li T, Chen KM, Ahmadi T, Lugtenburg PJ. Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an open-label, phase 1/2 study. Lancet. 2021 Sep 25;398(10306):1157-1169. Epub 2021 Sep 8. link to original article EuroPMC NCT03625037
##Update: Thieblemont C, Phillips T, Ghesquieres H, Cheah CY, Clausen MR, Cunningham D, Do YR, Feldman T, Gasiorowski R, Jurczak W, Kim TM, Lewis DJ, van der Poel M, Poon ML, Cota Stirner M, Kilavuz N, Chiu C, Chen M, Sacchi M, Elliott B, Ahmadi T, Hutchings M, Lugtenburg PJ. Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell-Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial. J Clin Oncol. 2023 Apr 20;41(12):2238-2247. Epub 2022 Dec 22. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC
==Glofitamab monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Dickinson et al. 2022 (NP30179)	2020-01 to 2021-09 	Phase 1/2 (RT)
====Immunotherapy====
*Glofitamab (Columvi) as follows:
**Cycle 1: 2.5 mg IV once on day 8, then 10 mg IV once on day 15
**Cycles 2 to 12: 30 mg IV once on day 1
====Immunosuppressive therapy====
*Obinutuzumab (Gazyva) as follows:
**Cycle 1: 1000 mg IV once on day 1
21-day cycle for 12 cycles
===References===
#NP30179: Dickinson MJ, Carlo-Stella C, Morschhauser F, Bachy E, Corradini P, Iacoboni G, Khan C, Wróbel T, Offner F, Trněný M, Wu SJ, Cartron G, Hertzberg M, Sureda A, Perez-Callejo D, Lundberg L, Relf J, Dixon M, Clark E, Humphrey K, Hutchings M. Glofitamab for Relapsed or Refractory Diffuse Large B-Cell Lymphoma. N Engl J Med. 2022 Dec 15;387(24):2220-2231. Epub 2022 Dec 11. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03075696
==131Iodine-Tositumomab monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence
Vose et al. 2000	1995-12-05 to 1996-11-20	Phase 2
Note: This was also evaluated in low-grade NHL but subtype was not specified. Now obsolete as this drug has been discontinued.
====Radioconjugate therapy, dosimetric step====
*On Day 0, infusions of:
**Tositumomab 450 mg IV over 1 hour
**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 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
===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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Lenalidomide monotherapy==
===Regimen===
Study 	Evidence
Witzig et al. 2011 (NHL-003)	Phase 2
====Targeted therapy====
*Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21
28-day cycles
===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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00413036
==Lenalidomide & Rituximab (R2)==
===Regimen===
Study 	Dates of enrollment	Evidence
Wang et al. 2013 (MDACC 2005-0461DLBCL)	2008-2011 	Phase 2, fewer than 20 pts in this subgroup
====Targeted therapy====
*Lenalidomide (Revlimid) 20 mg PO once per day on days 1 to 21
*Rituximab (Rituxan) as follows:
**Cycle 1: 375 mg/m2 IV once per day on days 1, 8, 15, 22
28-day cycles
===References===
# MDACC 2005-0461DLBCL: 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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00294632
==Lenalidomide & Tafasitamab==
===Regimen===
Study 	Dates of enrollment	Evidence
Salles et al. 2020 (L-MIND)	2016-2017 	Phase 2 (RT)
====Targeted therapy====
*Lenalidomide (Revlimid) as follows:
**Cycles 1 to 12: 25 mg PO once per day on days 1 to 21
*Tafasitamab (Monjuvi) as follows:
**Cycle 1: 12 mg/kg IV over 2 hours once per day on days 1, 4, 8, 15, 22
**Cycles 2 & 3: 12 mg/kg IV over 2 hours once per day on days 1, 8, 15, 22
**Cycle 4 onwards: 12 mg/kg IV over 2 hours once per day on days 1 & 15
28-day cycles
===References===
# 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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02399085
==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====
*Lisocabtagene maraleucel (Breyanzi) target dose of 100 x 106 CAR T cells IV once on day 0
One course
===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. link to original article dosing details in abstract have been reviewed by our editors EuroPMC 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. link to original article EuroPMC
==Loncastuximab tesirine monotherapy==
===Regimen===
FDA-recommended dose
Study 	Dates of enrollment	Evidence
Caimi et al. 2021 (LOTIS-2)	2018-2019 	Phase 2 (RT)
====Antibody-drug conjugate therapy====
*Loncastuximab tesirine (Zynlonta) as follows:
**Cycles 1 & 2: 0.15 mg/kg IV over 30 minutes once on day 1
**Cycles 3 to 18: 0.075 mg/kg IV over 30 minutes once on day 1
====Supportive therapy====
*Dexamethasone (Decadron) 4 mg IV or PO twice per day on days -1 to 2 (3 days total)
21-day cycle for up to 18 cycles (1 year)
===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. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT03589469
==OFAR==
OFAR: Oxaliplatin, Fludarabine, Ara-C (Cytarabine), Rituximab
===Regimen===
Study 	Dates of enrollment	Evidence 	Efficacy
Tsimberidou et al. 2008	2004-2006 	Phase 1/2	Likely has true ORR > 20%
Note: the manuscript does not specify what sequence the rituximab is given in.
====Chemotherapy====
*Oxaliplatin (Eloxatin) 25 mg/m2 IV over 2 hours once per day on days 1 to 4, given first (see note)
*Fludarabine (Fludara) 30 mg/m2 IV once per day on days 2 & 3, given second, within 30 minutes of completion of oxaliplatin (see note)
*Cytarabine (Ara-C) 1000 mg/m2 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/m2 IV over 4 to 6 hours once on day 3 
**Cycles 2 to 6: 375 mg/m2 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
===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. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
==Pembrolizumab monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Efficacy
Ding et al. 2017 (MC1485)	2015-02 to 2016-06 	Phase 2, fewer than 20 pts in this subgroup	Unlikely to have true ORR > 20%
====Immunotherapy====
*Pembrolizumab (Keytruda) 200 mg IV once on day 1
21-day cycle for up to 35 cycles (2 years)
===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. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT02332980
==R-DHAP==
R-DHAP: Rituximab, Dexamethasone, High-dose Ara-C (Cytarabine), Platinol (Cisplatin)
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Crump et al. 2014 (NCIC-CTG LY.12)	2003-2011 	Phase 3 (C)	R-GDP 	Not reported
====Targeted therapy====
*Rituximab (Rituxan) 375 mg/m2 IV once on day 1
====Glucocorticoid therapy====
*Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
====Chemotherapy====
*Cytarabine (Ara-C) 2000 mg/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===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC 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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==R-EPOCH==
R-EPOCH: Rituximab, Etoposide, Prednisone, Oncovin (Vincristine), Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin)
===Regimen===
Study 	Evidence
Jermann et al. 2004	Phase 2, fewer than 20 pts in this subgroup
Note: this is not the dose-adjusted R-EPOCH regimen
====Targeted therapy====
*Rituximab (Rituxan) 375 mg/m2 IV once on day 1
====Chemotherapy====
*Etoposide (Vepesid) 65 mg/m2/day IV continuous infusion over 72 hours, started on day 2 (total dose per cycle: 195 mg/m2)
*Vincristine (Oncovin) 0.5 mg/m2/day IV continuous infusion over 72 hours, started on day 2 (total dose per cycle: 1.5 mg/m2)
*Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 5
*Doxorubicin (Adriamycin) 15 mg/m2/day IV continuous infusion over 72 hours, started on day 2 (total dose per cycle: 45 mg/m2)
====Glucocorticoid therapy====
*Prednisone (Sterapred) 60 mg/m2/day PO on days 1 to 14
21-day cycle for 4 to 6 cycles
===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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==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 (E-switch-ic)	R-DHAP 	Not reported
====Targeted therapy====
*Rituximab (Rituxan) 375 mg/m2 IV once on day 1
====Chemotherapy====
*Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
*Cisplatin (Platinol) 75 mg/m2 IV once on day 1
====Glucocorticoid therapy====
*Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
21-day cycle for up to 3 cycles
====Subsequent treatment====
*NCIC-CTG LY.12, responders: autologous HSCT consolidation
===References===
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC 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. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Selinexor monotherapy==
===Regimen===
FDA-recommended dose
Study 	Dates of enrollment	Evidence
Kalakonda et al. 2020 (SADAL)	2015-2019 	Phase 2b (RT)
====Targeted therapy====
*Selinexor (Xpovio) 60 mg PO once per day on days 1 & 3
7-day cycles
===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. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT02227251
==Tisagenlecleucel monotherapy==
===Regimen===
FDA-recommended dose
Study 	Dates of enrollment 	Evidence 	Efficacy
Schuster et al. 2018 (JULIET)	2015-07-29 to 2017-11-02	Phase 2 (RT)	ORR: 59% (95% CI, 44-72)
Note: The FDA-recommended range is 0.6 to 6 x 108 CTL019 transduced viable T-cells.
====Preceding treatment====
*Lymphodepletion with FC or Bendamustine
====Immunotherapy====
*Tisagenlecleucel (Kymriah) 1 to 5 x 108 CTL019 transduced viable T-cells IV once on day 0
One course
===References===
# 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. link to original article dosing details in supplement have been reviewed by our editors EuroPMC 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. link to original article EuroPMC
=Consolidation after salvage therapy=
==BFR, then allo HSCT==
BFR: Bendamustine, Fludarabine, Rituximab
===Regimen===
Study 	Dates of enrollment	Evidence
Khouri et al. 2014 (MDACC 2008-0246)	2009-04 to 2013-02 	Phase 2, fewer than 20 pts in this subgroup
===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. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00880815
Category:Transformed lymphoma regimens
Category:Disease-specific pages
Category:Aggressive non-Hodgkin lymphomas
Category:Non-Hodgkin lymphomas