Transformed lymphoma

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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 (Treanda)

Regimen, Friedberg et al. 2008

Phase II, <20 patients reported

• Bendamustine (Treanda) 120 mg/m2 IV over 60 to 120 minutes once on days 1 & 2

21-day cycle x 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 (Revlimid)

Regimen, Wiernik et al. 2008 (NHL-002); Witzig et al. 2011 (NHL-003)

Phase II

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

28-day cycles until disease progression or unacceptable toxicity

References

1. Wiernik PH, Lossos IS, Tuscano JM, Justice G, Vose JM, Cole CE, Lam W, McBride K, Wride K, Pietronigro D, Takeshita K, Ervin-Haynes A, Zeldis JB, Habermann TM. Lenalidomide monotherapy in relapsed or refractory aggressive non-Hodgkin's lymphoma. J Clin Oncol. 2008 Oct 20;26(30):4952-7. Epub 2008 Jul 7. link to original article contains verified protocol PubMed
2. 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

Regimen, Wang et al. 2013

Phase II, <20 patients reported

• 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

OFAR: Oxaliplatin, Fludarabine, Ara-C, Rituximab

Regimen, Tsimberidou et al. 2008

Phase II

• 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) 375 mg/m2 IV over 4 to 6 hours once on day 3 of cycle 1; then 375 mg/m2 IV over 4 to 6 hours once on day 1 of cycles 2 to 6

Supportive medications:

• Pegfilgrastim (Neulasta) 6 mg SC once on day 6
• Herpes zoster and PCP (Pneumocystis jiroveci pneumonia) prophylaxis used

28-day cycles x 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

R-DHAP

R-DHAP: Rituximab, Dexamethasone, High-dose Ara-C (cytarabine), Platinol (cisplatin)

Regimen #1, Crump et al. 2014 (NCIC-CTG LY.12)

Phase III

• 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 x 2 doses on day 2 (total of 2 doses)
• Cisplatin (Platinol) 100 mg/m2 IV continuous infusion over 24 hours on day 1

21-day cycles x 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

R-EPOCH

R-EPOCH: Rituximab, Etoposide, Prednisone, Oncovin, Cyclophosphamide, Hydroxydaunorubicin

Regimen, Jermann et al. 2004

Phase II, <20 patients reported

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

• Rituximab (Rituxan) 375 mg/m2 IV on day 1
• Etoposide (Vepesid) 65 mg/m2/day (total dose of 195 mg/m2) IV continuous infusion on days 2 to 4
• Prednisone (Sterapred) 60 mg/m2/day PO on days 1 to 14
• Vincristine (Oncovin) 0.5 mg/m2/day (total dose of 1.5 mg/m2) IV continuous infusion on days 2 to 4
• Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 5
• Doxorubicin (Adriamycin) 15 mg/m2/day (total dose of 45 mg/m2) IV continuous infusion on days 2 to 4

21-day cycles x 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

R-GDP: Rituximab, Gemcitabine, Dexamethasone, Platinol

Regimen #1, Crump et al. 2014 (NCIC-CTG LY.12)

Phase III

• 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 cycles x 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