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

Grzegorz S. Nowakowski, Betsy LaPlant, William R. Macon, Craig B. Reeder, James M. Foran, Garth D. Nelson, Carrie A. Thompson, Candido E. Rivera, David J. Inwards, Ivana N. Micallef, Patrick B. Johnston, Luis F. Porrata, Stephen M. Ansell, Randy D. Gascoyne, Thomas M. Habermann, Thomas E. Witzig

Research output: Contribution to journalArticlepeer-review

243 Scopus citations

Abstract

Purpose: Lenalidomide has significant single-agent activity in relapsed diffuse large B-cell lymphoma (DLBCL). We demonstrated that lenalidomide can be safely combined with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone); this new combination is known as R2CHOP. The goal of this phase II study was to evaluate the efficacy of this combination in newly diagnosed DLBCL. Patients and Methods: Eligible patients were adults with newly diagnosed untreated stages II to IV CD20+ DLBCL. Patients received lenalidomide 25 mg orally per day on days 1 through 10 with standard-dose R-CHOP every 21 days for six cycles. All patients received pegfilgrastim on day 2 of each cycle and aspirin prophylaxis throughout. DLBCL molecular subtype was determined by tumor immunohistochemistry and classified as germinal center B-cell (GCB) versus non-GCB in the R2CHOP patients and 87 control patients with DLBCL from the Lymphoma Database who were treated with conventional R-CHOP. Results: In all, 64 patients with DLBCL were enrolled, and 60 were evaluable for response. The overall response rate was 98% (59 of 60) with 80% (48 of 60) achieving complete response. Event-free survival and overall survival (OS) rates at 24 months were 59% (95% CI, 48% to 74%) and 78% (95% CI, 68% to 90%), respectively. In R-CHOP patients, 24-month progression-free survival (PFS) and OS were 28% versus 64% (P < .001) and 46% versus 78% (P < .001) in non-GCB DLBCL versus GCB DLBCL, respectively. In contrast, there was no difference in 24-month PFS or OS for R2CHOP patients on the basis of non-GCB and GCB subtype (60% v 59% [P = .83] and 83% v 75% [P = .61] at 2 years, respectively). Conclusion: R2CHOP shows promising efficacy in DLBCL. The addition of lenalidomide appears to mitigate a negative impact of non-GCB phenotype on patient outcome.

Original languageEnglish (US)
Pages (from-to)251-257
Number of pages7
JournalJournal of Clinical Oncology
Volume33
Issue number3
DOIs
StatePublished - Jan 20 2015

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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