Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Lymphoma

Lenalidomide can be safely combined with R-CHOP (R2CHOP) in the initial chemotherapy for aggressive B-cell lymphomas: phase I study

Abstract

Lenalidomide was shown to have significant single-agent activity in relapsed aggressive non-Hodgkin's lymphoma (NHL). We conducted a phase I trial to establish the maximum tolerated dose of lenalidomide that could be combined with R-CHOP (rituximab–cyclophosphamide, doxorubicin, vincristine, and prednisone). Eligible patients were adults with newly diagnosed, untreated CD20 positive diffuse large cell or follicular grade III NHL. Patients received oral lenalidomide on days 1–10 with standard dose R-CHOP every 21 days. All patients received pegfilgrastim on day 2 of the cycle and aspirin prophylaxis. The lenalidomide dose levels tested were 15, 20 and 25 mg. A total of 24 patients were enrolled. The median age was 65 (35–82) years and 54% were over 60 years. Three patients received 15 mg, 3 received 20 mg and 18 received 25 mg of lenalidomide. No dose limiting toxicity was found, and 25 mg on days 1–10 is the recommended dose for phase II. The incidence of grade IV neutropenia and thrombocytopenia was 67% and 21%, respectively. Febrile neutropenia was rare (4%) and there were no toxic deaths. The overall response rate was 100% with a complete response rate of 77%. Lenalidomide at the dose of 25 mg/day administered on days 1 to 10 of 21-day cycle can be safely combined with R-CHOP in the initial chemotherapy of aggressive B-cell lymphoma.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 2002; 346: 235–242.

    Article  CAS  PubMed Central  Google Scholar 

  2. Habermann TM, Weller EA, Morrison VA, Gascoyne RD, Cassileth PA, Cohn JB et al. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol 2006; 24: 3121–3127.

    Article  CAS  PubMed Central  Google Scholar 

  3. Sehn LH, Donaldson J, Chhanabhai M, Fitzgerald C, Gill K, Klasa R et al. Introduction of combined CHOP plus rituximab therapy dramatically improved outcome of diffuse large B-cell lymphoma in British Columbia. J Clin Oncol 2005; 23: 5027–5033.

    Article  CAS  Google Scholar 

  4. Pfreundschuh M, Trumper L, Osterborg A, Pettengell R, Trneny M, Imrie K et al. 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; 7: 379–391.

    Article  CAS  PubMed Central  Google Scholar 

  5. Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Ferme C et al. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d’Etude des Lymphomes de l’Adulte. J Clin Oncol 2005; 23 (18): 4117–4126.

    Article  CAS  PubMed Central  Google Scholar 

  6. Klimo P, Connors JM . MACOP-B chemotherapy for the treatment of diffuse large-cell lymphoma. Ann Intern Med 1985; 102: 596–602.

    Article  CAS  Google Scholar 

  7. Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM et al. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. N Engl J Med 1993; 328: 1002–1006.

    Article  CAS  Google Scholar 

  8. Gordon LI, Harrington D, Andersen J, Colgan J, Glick J, Neiman R et al. Comparison of a second-generation combination chemotherapeutic regimen (m-BACOD) with a standard regimen (CHOP) for advanced diffuse non-Hodgkin's lymphoma. N Eng J Med 1992; 327: 1342–1349.

    Article  CAS  Google Scholar 

  9. Cooper IA, Wolf MM, Robertson TI, Fox RM, Matthews JP, Stone JM et al. Randomized comparison of MACOP-B with CHOP in patients with intermediate-grade non-Hodgkin's lymphoma. The Australian and New Zealand Lymphoma Group. J Clin Oncol 1994; 12: 769–778.

    Article  CAS  Google Scholar 

  10. Sertoli MR, Santini G, Chisesi T, Congiu AM, Rubagotti A, Contu A et al. MACOP-B versus ProMACE-MOPP in the treatment of advanced diffuse non-Hodgkin's lymphoma: results of a prospective randomized trial by the non-Hodgkin's Lymphoma Cooperative Study Group. J Clin Oncol 1994; 12: 1366–1374.

    Article  CAS  Google Scholar 

  11. Wiernik PH, Lossos IS, Tuscano JM, Justice G, Vose JM, Cole CE et al. Lenalidomide monotherapy in relapsed or refractory aggressive non-Hodgkin's lymphoma. J Clin Oncol 2008; 26: 4952–4957.

    Article  PubMed Central  Google Scholar 

  12. Ivanov V, Tabouret E, Chuto G, Chetaille B, Fezoui H, Coso D et al. Rituximab-lenalidomide-dexamethasone induces complete and durable remission in relapsed refractory diffuse large B-cell non-Hodgkin lymphoma. Leuk Lymphoma 2010; 51: 1758–1760.

    Article  CAS  Google Scholar 

  13. Witzig TE, Vose JM, Zinzani PL, Reeder CB, Buckstein R, Polikoff JA et al. An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-Cell non-Hodgkin lymphoma. Ann Oncol 2011, (e-pub ahead of print).

  14. Haslett PA, Hanekom WA, Muller G, Kaplan G . Thalidomide and a thalidomide analogue drug costimulate virus-specific CD8+ T cells in vitro. J Infect Dis 2003; 187: 946–955.

    Article  CAS  Google Scholar 

  15. Zhang H, Vakil V, Braunstein M, Smith EL, Maroney J, Chen L et al. Circulating endothelial progenitor cells in multiple myeloma: implications and significance. Blood 2005; 105: 3286–3294.

    Article  CAS  Google Scholar 

  16. Pellagatti A, Jadersten M, Forsblom AM, Cattan H, Christensson B, Emanuelsson EK et al. Lenalidomide inhibits the malignant clone and up-regulates the SPARC gene mapping to the commonly deleted region in 5q- syndrome patients. Proc Natl Acad Sci USA 2007; 104: 11406–11411.

    Article  CAS  PubMed Central  Google Scholar 

  17. Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ et al. Revised response criteria for malignant lymphoma. J Clin Oncol 2007; 25: 579–586.

    Article  PubMed Central  Google Scholar 

  18. Zhang L, Qian Z, Cai Z, Sun L, Wang H, Bartlett JB et al. Synergistic antitumor effects of lenalidomide and rituximab on mantle cell lymphoma in vitro and in vivo. Am J Hematol 2009; 84: 553–559.

    Article  CAS  PubMed Central  Google Scholar 

  19. Richardson PG, Schlossman RL, Weller E, Hideshima T, Mitsiades C, Davies F et al. Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma. Blood 2002; 100: 3063–3067.

    Article  CAS  Google Scholar 

  20. Lu L, Payvandi F, Wu L, Zhang LH, Hariri RJ, Man HW et al. The anti-cancer drug lenalidomide inhibits angiogenesis and metastasis via multiple inhibitory effects on endothelial cell function in normoxic and hypoxic conditions. Mic Res 2009; 77: 78–86.

    Article  CAS  Google Scholar 

  21. Wu L, Adams M, Carter T, Chen R, Muller G, Stirling D et al. Lenalidomide enhances natural killer cell and monocyte-mediated antibody-dependent cellular cytotoxicity of rituximab-treated CD20+ tumor cells. Clin Cancer Res 2008; 14: 4650–4657.

    Article  CAS  Google Scholar 

  22. Smith TJ, Khatcheressian J, Lyman GH, Ozer H, Armitage JO, Balducci L et al. 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol 2006; 24: 3187–3205.

    Article  CAS  Google Scholar 

  23. Czuczman MS . CHOP plus rituximab chemoimmunotherapy of indolent B-cell lymphoma. Semin oncol 1999; 26 (5 Suppl): 88–96.

    CAS  PubMed  Google Scholar 

  24. Rajkumar SV, Blood E . Lenalidomide and venous thrombosis in multiple myeloma. N Eng J Med 2006; 354: 2079–2080.

    Article  Google Scholar 

  25. Zonder JA, Barlogie B, Durie BG, McCoy J, Crowley J, Hussein MA . Thrombotic complications in patients with newly diagnosed multiple myeloma treated with lenalidomide and dexamethasone: benefit of aspirin prophylaxis. Blood 2006; 108: 403, author reply 404.

    Article  CAS  Google Scholar 

  26. Caruso V, Di Castelnuovo A, Meschengieser S, Lazzari MA, de Gaetano G, Storti S et al. Thrombotic complications in adult patients with lymphoma: a meta-analysis of 29 independent cohorts including 18018 patients and 1149 events. Blood 2010; 115: 5322–5328.

    Article  CAS  Google Scholar 

  27. Morton LM, Wang SS, Devesa SS, Hartge P, Weisenburger DD, Linet MS . Lymphoma incidence patterns by WHO subtype in the United States, 1992–2001. Blood 2006; 107: 265–276.

    Article  CAS  PubMed Central  Google Scholar 

  28. Habermann TM, Lossos IS, Justice G, Vose JM, Wiernik PH, McBride K et al. Lenalidomide oral monotherapy produces a high response rate in patients with relapsed or refractory mantle cell lymphoma. Br J Haematol 2009; 145: 344–349.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to G S Nowakowski or T E Witzig.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nowakowski, G., LaPlant, B., Habermann, T. et al. Lenalidomide can be safely combined with R-CHOP (R2CHOP) in the initial chemotherapy for aggressive B-cell lymphomas: phase I study. Leukemia 25, 1877–1881 (2011). https://doi.org/10.1038/leu.2011.165

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2011.165

Keywords

This article is cited by

Search

Quick links