Transformed lymphoma

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J.C. Villasboas Bisneto, MD
Rochester, MN
11 regimens on this page
11 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

Axicabtagene ciloleucel monotherapy

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Regimen

FDA-recommended dose
Study Evidence Efficacy
Nellapu et al. 2017 (ZUMA-1) Phase II, <20 pts in subgroup ORR: 82%

Chemotherapy

Treatment followed by:

Cellular therapy

Supportive medications

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

References

  1. Phase 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 PubMed
  2. 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. link to original article contains verified protocol PubMed

Bendamustine monotherapy

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Regimen

Study Evidence
Friedberg et al. 2008 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

131Iodine-Tositumomab monotherapy

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Regimen

Study Evidence
Vose et al. 2000 Phase II

Also evaluated in low-grade NHL but subtype was not specified. Now obsolete as this drug has been discontinued.

Dosimetric step

  • On Day 0, infusions of:
  • Day 2, 3, or 4: Second scan of whole body dosimetry & redistribution
  • Day 6 or 7: Third scan of whole body dosimetry & redistribution

Therapeutic step

Calculated dose of I-131 is based on information from serial total-body gamma-camera counts

References

  1. 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 contains verified protocol PubMed

Lenalidomide monotherapy

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Regimen

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

Chemotherapy

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 Phase II, <20 pts in this subgroup

Chemotherapy

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

Supportive medications

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 Phase II, <20 pts in this subgroup 44%

Immunotherapy

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

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 Phase II, <20 pts in this subgroup

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

Chemotherapy

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

21-day cycle for up to 3 cycles

Responders proceeded to undergo autologous stem cell transplant.

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 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

Tisagenlecleucel monotherapy

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Regimen

FDA-recommended dose
Study Evidence Efficacy
Schuster et al. 2017 (CCTL019C2201) Phase II ORR: 59% (95% CI, 44‐72)

The range given is the FDA-recommended dose.

Preceding treatment

Immunotherapy

One course

References

  1. Abstract: Schuster SJ, Bishop MR, Tam C, et al. Global Pivotal Phase 2 Trial of the CD19‐Targeted Therapy CTL019 in Adult Patients with Relapsed or Refractory (R/R) Diffuse Large B‐Cell Lymphoma (DLBCL)—an Interim Analysis. Hematological Oncology. 2017;35(S2):27. link to abstract