A phase 2/3 multicenter, randomized, open-label study to compare the efficacy and safety of lenalidomide versus investigator's choice in patients with relapsed or refractory diffuse large B-cell lymphoma

Myron S. Czuczman, Marek Trněný, Andrew Davies, Simon Rule, Kim M. Linton, Nina Wagner-Johnston, Randy D. Gascoyne, Graham W. Slack, Pierre Brousset, David A. Eberhard, Francisco J. Hernandez-Ilizaliturri, Gilles Salles, Thomas E. Witzig, Pier Luigi Zinzani, George W. Wright, Louis M. Staudt, Yandan Yang, P. Mickey Williams, Chih Jian Lih, Jacqueline RussoAnjan Thakurta, Patrick Hagner, Pierre Fustier, Dale Song, Ian D. Lewis

Research output: Contribution to journalArticle

Abstract

Purpose: Randomized, multicenter, open-label, phase 2/3 trial investigating lenalidomide versus investigator's choice (IC) in relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Experimental Design: Patients with DLBCL who received ≥2 prior therapies were stratified by DLBCL subtype [germinal center B-cell (GCB) vs. non-GCB; determined by immunohistochemistry (IHC)] and then randomized 1:1 to lenalidomide (25 mg/day, 21 days of 28-day cycle) or IC (gemcitabine, rituximab, etoposide, or oxaliplatin). Crossover to lenalidomide was permitted for IC-treated patients with radiologically confirmed progressive disease. The primary endpoint was overall response rate (ORR). Progression-free survival (PFS), overall survival, and subtype analysis [GCB vs. activated B-cell (ABC)] using gene expression profiling (GEP) were exploratory endpoints. Results: Stage 1: 102 DLBCL patients (by IHC: non-GCB, n = 54; GCB, n = 48) received ≥1 dose of lenalidomide or IC. Hematologic treatment-emergent adverse events with lenalidomide versus IC included neutropenia (42.6%; 36.4%), anemia (33.3%; 47.3%), thrombocytopenia (24.1%; 43.6%), and leukopenia (5.6%; 12.7%), respectively. Overall, lenalidomide-treated patients had an ORR of 27.5% versus 11.8% in IC (ORRs were similar regardless of IHC-defined DLBCL subtype). Median PFS was increased in patients receiving lenalidomide (13.6 weeks) versus IC (7.9 weeks; P = 0.041), with greater improvements in non-GCB patients (15.1 vs. 7.1 weeks, respectively; P = 0.021) compared with GCB (10.1 vs. 9.0 weeks, respectively; P = 0.550). Conclusions: The clinical benefit of lenalidomide monotherapy in DLBCL patients was more evident in the non-GCB subtype. Exploratory analyses suggest that this preferential benefit was more pronounced in the GEP-defined ABC population, demonstrating a need for additional studies of lenalidomide in DLBCL using GEP subtyping.

Original languageEnglish (US)
Pages (from-to)4127-4137
Number of pages11
JournalClinical Cancer Research
Volume23
Issue number15
DOIs
StatePublished - Aug 1 2017

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Czuczman, M. S., Trněný, M., Davies, A., Rule, S., Linton, K. M., Wagner-Johnston, N., Gascoyne, R. D., Slack, G. W., Brousset, P., Eberhard, D. A., Hernandez-Ilizaliturri, F. J., Salles, G., Witzig, T. E., Zinzani, P. L., Wright, G. W., Staudt, L. M., Yang, Y., Williams, P. M., Lih, C. J., ... Lewis, I. D. (2017). A phase 2/3 multicenter, randomized, open-label study to compare the efficacy and safety of lenalidomide versus investigator's choice in patients with relapsed or refractory diffuse large B-cell lymphoma. Clinical Cancer Research, 23(15), 4127-4137. https://doi.org/10.1158/1078-0432.CCR-16-2818