Transformed lymphoma

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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.

All lines of therapy

Bendamustine monotherapy

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Regimen

Study	Evidence
Friedberg et al. 2008	Pilot"|Phase II, <20 pts in this subgroup

Chemotherapy

Note: these infusion instructions are for the Treanda formulation, which was discontinued on 3/31/2016.

• Bendamustine 120 mg/m² IV over 60 to 120 minutes once per day on days 1 & 2

21-day cycle for up to 12 cycles

References

1. 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 contains verified protocol PubMed

Lenalidomide monotherapy

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Regimen

Study	Evidence
Witzig et al. 2011 (NHL-003	Phase II

Chemotherapy

• Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21

28-day cycles until disease progression or unacceptable toxicity

References

1. 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 contains verified protocol PubMed

Lenalidomide & Rituximab

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Regimen

Study	Evidence
Wang et al. 2013	Pilot"|Phase II, <20 pts in this subgroup

Chemotherapy

• Lenalidomide (Revlimid) 20 mg PO once per day on days 1 to 21
• Rituximab (Rituxan) 375 mg/m² IV once per week on weeks 1 to 4 of cycle 1, only

28-day cycles

References

1. 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 contains verified protocol PubMed

OFAR

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OFAR: Oxaliplatin, Fludarabine, Ara-C (Cytarabine), Rituximab

Regimen

Study	Evidence
Tsimberidou et al. 2008	Phase II

Chemotherapy

• Oxaliplatin (Eloxatin) 25 mg/m² IV over 2 hours once per day on days 1 to 4
• Fludarabine (Fludara) 30 mg/m² IV once per day on days 2 & 3, adminstered within 30 minutes of completion of Oxaliplatin (Eloxatin)
• Cytarabine (Cytosar) 1000 mg/m² IV over 2 hours once per day on days 2 & 3, 4 hours after Fludarabine (Fludara) started
• Rituximab (Rituxan) as follows:
  • 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 medications

• 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

1. 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 contains protocol PubMed

Pembrolizumab monotherapy

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Regimen

Study	Evidence	ORR
Ding et al. 2017	Pilot"|Phase II, <20 pts in this subgroup	44%

Immunotherapy

• Pembrolizumab (Keytruda) 200 mg IV once on day 1

21-day cycle for up to 2 years

References

1. 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 contains verified protocol link to PMC article PubMed

R-DHAP

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

Regimen

Study	Evidence	Comparator	Efficacy
Crump et al. 2014 (NCIC-CTG LY.12)	Phase III	R-GDP	Not reported

Chemotherapy

• Rituximab (Rituxan) 375 mg/m² IV once on day 1
• Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
• Cytarabine (Cytosar) 2000 mg/m² IV over 3 hours Q12H on day 2 (total of 2 doses)
• Cisplatin (Platinol) 100 mg/m² IV continuous infusion over 24 hours on day 1

21-day cycle for up to 3 cycles

References

1. 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 verified protocol PubMed
   1. 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 contains verified protocol PubMed

R-EPOCH

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

Regimen

Study	Evidence
Jermann et al. 2004	Pilot"|Phase II, <20 pts in this subgroup

Note: this is not the dose-adjusted R-EPOCH regimen

Chemotherapy

• Rituximab (Rituxan) 375 mg/m² IV once on day 1
• Etoposide (Vepesid) 65 mg/m²/day IV continuous infusion on days 2 to 4 (total dose per cycle: 195 mg/m²)
• Prednisone (Sterapred) 60 mg/m²/day PO on days 1 to 14
• Vincristine (Oncovin) 0.5 mg/m²/day IV continuous infusion on days 2 to 4 (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 on days 2 to 4 (total dose per cycle: 45 mg/m²)

21-day cycle for 4 to 6 cycles

References

1. 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 contains verified protocol PubMed

R-GDP

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

Regimen

Study	Evidence	Comparator	Efficacy
Crump et al. 2014 (NCIC-CTG LY.12)	Phase III	R-DHAP	Not reported

Chemotherapy

• Rituximab (Rituxan) 375 mg/m² IV once on day 1
• Gemcitabine (Gemzar) 1000 mg/m² IV once per day on days 1 & 8
• Dexamethasone (Decadron) 40 mg PO once per day on days 1 to 4
• Cisplatin (Platinol) 75 mg/m² IV once on day 1

21-day cycle for up to 3 cycles

Responders proceeded to undergo autologous stem cell transplant.

References

1. 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 verified protocol PubMed
   1. 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 contains verified protocol PubMed