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.

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.

• Authors: 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 Russo, Anjan Thakurta, Patrick Hagner, Pierre Fustier, Dale Song, Ian D Lewis
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 23 Issue 15 Pg. 4127-4137 (Aug 01 2017) ISSN: 1557-3265 [Electronic] United States
• PMID: 28381416 (Publication Type: Clinical Trial, Phase II, Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: ©2017 American Association for Cancer Research.

Chemical References

• Organoplatinum Compounds
• Oxaliplatin
• Deoxycytidine
• Rituximab
• Thalidomide
• Etoposide
• Lenalidomide
• Gemcitabine

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Disease-Free Survival
• Etoposide (administration & dosage)
• Female
• Humans
• Kaplan-Meier Estimate
• Lenalidomide
• Lymphoma, Large B-Cell, Diffuse (drug therapy, pathology)
• Male
• Middle Aged
• Organoplatinum Compounds (administration & dosage)
• Oxaliplatin
• Prognosis
• Proportional Hazards Models
• Rituximab (administration & dosage)
• Thalidomide (administration & dosage, adverse effects, analogs & derivatives)
• Treatment Outcome
• Gemcitabine