Czuczman, Myron S., Trněný, Marek, Davies, Andrew, Rule, Simon, Linton, Kim M., Wagner-Johnston, Nina, Gascoyne, Randy D., Slack, Graham W, Brousset, Pierre, Eberhard, David A., Hernandez-Ilizaliturri, Francisco J., Salles, Gilles, Witzig, Thomas E., Zinzani, Pier Luigi, Wright, George W., Staudt, Louis M., Yang, Yandan, Williams, P. Mickey, Lih, Chih-Jian, Russo, Jacqueline, Thakurta, Anjan, Hagner, Patrick, Fustier, Pierre, Song, Dale and Lewis, Ian 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. (doi:10.1158/1078-0432.CCR-16-2818).
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. Clin Cancer Res; 23(15); 4127-37. ©2017 AACR.
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