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.

  • Letter to the Editor
  • Published:

A phase II randomized study of lenalidomide or lenalidomide and rituximab as maintenance therapy following standard chemotherapy for patients with high/high-intermediate risk diffuse large B-cell lymphoma

Leukemia volume 31, pages 241–244 (2017)Cite this article

Subjects

Diffuse large B-cell lymphoma (DLBCL) is curable in about two-third of patients with rituximab, cyclophosphamide, adriamycin, vincristine, prednisone (R-CHOP) immunochemotherapy. Risk stratification of DLBCL that employs the International Prognostic Index (IPI) is a robust predictive prognostic model, developed more than two decades ago and grouped patients into four categories with a 2-year survival of 34% in the highest risk group.1 The revised IPI confirmed the prognostic ability of these factors in the rituximab era, stratifying the outcome of patients using similar prognostic markers and regrouping patients into three categories: patients with three or more risk factors had the worst progression free survival (PFS) of 53%.2 Despite overall improvements with rituximab, the prognosis continues to remain poor in patients with high-risk features.

Lenalidomide is an oral immunomodulator with direct anti-tumor activity and indirect anti-neoplastic actions through its immunologic effects. Our group and others previously showed that len induces antiproliferative effects against lymphoma cell lines.3, 4 Increased number and functional activity of natural-killer cells were demonstrated in pre-clinical models treated with len.5 The anti-tumor effects of len were augmented by rituximab-associated antibody-dependent cellular cytotoxicity.6

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1

References

  1. A predictive model for aggressive non-Hodgkin's lymphoma. The International Non-Hodgkin's Lymphoma Prognostic Factors Project. N Engl J Med 1993; 329: 987–994.

    Article  Google Scholar 

  2. Sehn LH, Berry B, Chhanabhai M, Fitzgerald C, Gill K, Hoskins P et al. The revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP. Blood 2007; 109: 1857–1861.

    Article  CAS  Google Scholar 

  3. Hernandez-Ilizaliturri FJ, Reddy N, Holkova B, Ottman E, Czuczman MS . Immunomodulatory drug CC-5013 or CC-4047 and rituximab enhance antitumor activity in a severe combined immunodeficient mouse lymphoma model. Clin Cancer Res 2005; 11: 5984–5992.

    Article  CAS  Google Scholar 

  4. Reddy N, Hernandez-Ilizaliturri FJ, Deeb G, Roth M, Vaughn M, Knight J et al. Immunomodulatory drugs stimulate natural killer-cell function, alter cytokine production by dendritic cells, and inhibit angiogenesis enhancing the anti-tumour activity of rituximab in vivo. Br J Haematol 2008; 140: 36–45.

    CAS  PubMed  Google Scholar 

  5. Zhu D, Corral LG, Fleming YW, Stein B . Immunomodulatory drugs Revlimid (lenalidomide) and CC-4047 induce apoptosis of both hematological and solid tumor cells through NK cell activation. Cancer Immunol Immunother 2008; 57: 1849–1859.

    Article  CAS  Google Scholar 

  6. 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 

  7. 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  Google Scholar 

  8. Recher C, Coiffier B, Haioun C, Molina TJ, Ferme C, Casasnovas O et al. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet 2011; 378: 1858–1867.

    Article  CAS  Google Scholar 

  9. Stiff PJ, Unger JM, Cook JR, Constine LS, Couban S, Stewart DA et al. Autologous transplantation as consolidation for aggressive non-Hodgkin's lymphoma. N Engl J Med 2013; 369: 1681–1690.

    Article  CAS  Google Scholar 

  10. Crump MLS, Fayad L, Lee J, Rocco AD . A Phase III study of enzastaurin in patients with high-risk diffuse large B cell lymphoma following response to primary treatment: the prelude trial. J Clin Oncol 2016; 34: 2484–2492.

    Article  CAS  Google Scholar 

  11. Hainsworth JD, Arrowsmith ER, McCleod M, Hsi ED, Hamid O, Shi P et al. A randomized, phase 2 study of R-CHOP plus enzastaurin vs R-CHOP in patients with intermediate- or high-risk diffuse large B-cell lymphoma. Leuk Lymphoma 2016; 57: 216–218.

    Article  Google Scholar 

  12. 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  Google Scholar 

  13. Vitolo U, Chiappella A, Franceschetti S, Carella AM, Baldi I, Inghirami G et al. Lenalidomide plus R-CHOP21 in elderly patients with untreated diffuse large B-cell lymphoma: results of the REAL07 open-label, multicentre, phase 2 trial. Lancet Oncol 2014; 15: 730–737.

    Article  CAS  Google Scholar 

  14. Nowakowski GS, LaPlant B, Macon WR, Reeder CB, Foran JM, Nelson GD et al. Lenalidomide combined with R-CHOP overcomes negative prognostic impact of non-germinal center B-cell phenotype in newly diagnosed diffuse large B-Cell lymphoma: a phase II study. J Clin Oncol 2015; 33: 251–257.

    Article  CAS  Google Scholar 

  15. Maurer MJ, Ghesquieres H, Jais JP, Witzig TE, Haioun C, Thompson CA et al. Event-free survival at 24 months is a robust end point for disease-related outcome in diffuse large B-cell lymphoma treated with immunochemotherapy. J Clin Oncol 2014; 32: 1066–1073.

    Article  Google Scholar 

Download references

Acknowledgements

This trial was supported in part by the NIH5k-12 CA090625-09 and Vanderbilt CTSA UL1 RR024975. This study has been presented at the American Society of Hematology meeting, 6th December 2015, Orlando, Florida, USA.

Author Contributions

Conception and design: NMR financial support: Celgene and grants; provision of study materials or patients: NMR, KLR, JPG, DSM and SP; collection and data assembly: NMR and HC.

Author information

Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

    N M Reddy, J P Greer & D S Morgan

  2. Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA

    H Chen

  3. Division of Hematology/Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA

    S I Park

  4. Division of Hematology/Oncology, Weill Cornell Medical College, New York, NY, USA

    K L Richards

Authors
  1. N M Reddy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J P Greer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D S Morgan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S I Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. K L Richards
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to N M Reddy.

Ethics declarations

Competing interests

NM Reddy: celgene, research support and advisory board; SI Park: research support from Teva and Seattle Genetics and travel support from Janssen; and the remaining authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on the Leukemia website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Reddy, N., Greer, J., Morgan, D. et al. A phase II randomized study of lenalidomide or lenalidomide and rituximab as maintenance therapy following standard chemotherapy for patients with high/high-intermediate risk diffuse large B-cell lymphoma. Leukemia 31, 241–244 (2017). https://doi.org/10.1038/leu.2016.255

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2016.255

This article is cited by

Search

Advanced search

Quick links