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

被引：184

作者：

Czuczman, Myron S. ^{[1
,20
]}

Trneny, Marek ^{[2
]}

Davies, Andrew ^{[3
]}

Rule, Simon ^{[4
]}

Linton, Kim M. ^{[5
]}

Wagner-Johnston, Nina ^{[6
]}

Gascoyne, Randy D. ^{[7
]}

Slack, Graham W. ^{[7
]}

Brousset, Pierre ^{[8
]}

Eberhard, David A. ^{[9
,10
]}

Hernandez-Ilizaliturri, Francisco J. ^{[1
]}

Salles, Gilles ^{[11
]}

Witzig, Thomas E. ^{[12
,13
]}

Zinzani, Pier Luigi ^{[14
]}

Wright, George W. ^{[15
]}

Staudt, Louis M. ^{[16
]}

Yang, Yandan ^{[16
]}

Williams, P. Mickey ^{[17
]}

Lih, Chih-Jian ^{[18
,19
]}

Russo, Jacqueline ^{[20
]}

Thakurta, Anjan ^{[20
]}

Hagner, Patrick ^{[20
]}

Fustier, Pierre ^{[21
]}

Song, Dale ^{[20
]}

Lewis, Ian D. ^{[22
,23
]}

机构：

[1] Roswell Pk Canc Inst, Buffalo, NY 14263 USA

[2] Charles Univ Hosp, Dept Hematol, Prague, Czech Republic

[3] Univ Southampton, Fac Med, Canc Sci Unit, Southampton, Hants, England

[4] Derriford Hosp, Dept Haematol, Plymouth, Devon, England

[5] Christie Fdn Trust, Div Mol & Clin Canc Sci, Manchester, Lancs, England

[6] Washington Univ, Sch Med, Div Oncol, St Louis, MO USA

[7] BC Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC, Canada

[8] CHU Purpan, Lab Anat Pathol, Toulouse, France

[9] Univ N Carolina, Dept Pathol Lab Med, Chapel Hill, NC USA

[10] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA

[11] Ctr Hosp Lyon Sud, Hos Civils Lyon, Hematol Dept, Pierre Benite, France

[12] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA

[13] Mayo Clin, Dept Haematol, Rochester, MN USA

[14] Univ Bologna, Inst Hematol & Med Oncol, Bologna, Italy

[15] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA

[16] NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[17] NCI, Mol Characterizat Lab, Frederick Natl Lab Canc Res, NIH, Frederick, MD 21701 USA

[18] Leidos Biomed Res Inc, Mol Characterizat & Clin Assay Dev Lab, Frederick, MD USA

[19] Frederick Natl Lab Canc Res, Frederick, MD USA

[20] Celgene Corp, Summit, NJ 07901 USA

[21] Celgene Corp, Boudry, Switzerland

[22] Royal Adelaide Hosp, Div Haematol, Adelaide, SA, Australia

[23] Univ Adelaide, Adelaide, SA, Australia

来源：

CLINICAL CANCER RESEARCH | 2017年 / 23卷 / 15期

关键词：

RITUXIMAB PLUS CYCLOPHOSPHAMIDE; GENE-EXPRESSION; SURVIVAL; THERAPY; CHEMOTHERAPY; VINCRISTINE; DOXORUBICIN; STRATEGIES; MUTATIONS; SUBTYPES;

D O I：

10.1158/1078-0432.CCR-16-2818

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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. (C) 2017 AACR.

引用

页码：4127 / 4137

页数：11

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