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Clin Cancer Res. 2017 Aug 1;23(15):4127-4137. doi: 10.1158/1078-0432.CCR-16-2818. Epub 2017 Apr 5.

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.

Author information

1
Roswell Park Cancer Institute, Buffalo, New York. mczuczman@celgene.com.
2
Department of Hematology, Charles University Hospital, Prague, Czech Republic.
3
Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
4
Department of Haematology, Derriford Hospital, Plymouth, United Kingdom.
5
Division of Molecular and Clinical Cancer Sciences, The Christie Foundation Trust, Manchester, United Kingdom.
6
Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
7
Centre for Lymphoid Cancers, BC Cancer Agency, Vancouver, British Columbia, Canada.
8
Laboratoire D'Anatomie Pathologique, Centre Hospitalier Universitaire Purpan, Toulouse, France.
9
Department of Pathology/Laboratory Medicine and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina.
10
Roswell Park Cancer Institute, Buffalo, New York.
11
Hematology Department, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Benite, France.
12
Departments of Laboratory Medicine and Pathology and Hematology, Mayo Clinic, Rochester, Minnesota.
13
Institute of Hematology and Medical Oncology, University of Bologna, Bologna, Italy.
14
Biometric Research Branch, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
15
Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
16
Molecular Characterization Laboratory, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, Maryland.
17
Molecular Characterization and Clinical Assay Development Laboratory, Leidos Biomedical Research Inc. and Frederick National Laboratory for Cancer Research, Frederick, Maryland.
18
Celgene Corporation, Summit, New Jersey.
19
Celgene Corporation, Boudry, Switzerland.
20
Divison of Haematology, Royal Adelaide Hospital and University of Adelaide, Adelaide, Australia.

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.

PMID:
28381416
DOI:
10.1158/1078-0432.CCR-16-2818
[Indexed for MEDLINE]
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