ROBUST: A Phase III Study of Lenalidomide Plus R-CHOP Versus Placebo Plus R-CHOP in Previously Untreated Patients With ABC-Type Diffuse Large B-Cell Lymphoma

作者：Grzegorz S. Nowakowski, Annalisa Chiappella, Randy D. Gascoyne, David W. Scott, Qingyuan Zhang, Wojciech Jurczak, Muhıt Özcan, Xiaonan Hong, Jun Zhu, Jie Jin, David Belada, Juan Bergua, Francesco Piazza, Heidi Móciková, Anna Lia Molinari, Dok Hyun Yoon, Federica Cavallo, Monica Tani, Kazuhito Yamamoto, Koji Izutsu, Koji Kato, Myron S. Czuczman, Sarah Hersey, Adrian Kilcoyne, Jacqueline Russo, Krista Hudak, Jingshan Zhang, Steve Wade, Thomas E. Witzig, Umberto Vitolo · 发表于：Journal of Clinical Oncology · 年份：2021 · DOI：10.1200/jco.20.01366 · 被引用次数：276 · 研究领域：Lymphoma Diagnosis and Treatment、CAR-T cell therapy research、CNS Lymphoma Diagnosis and Treatment

PURPOSE Patients with the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) historically showed inferior survival with standard rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Phase II studies demonstrated that adding the immunomodulatory agent lenalidomide to R-CHOP improved outcomes in ABC-type DLBCL. The goal of the global, phase III ROBUST study was to compare lenalidomide plus R-CHOP (R2-CHOP) with placebo/R-CHOP in previously untreated, ABC-type DLBCL. METHODS Histology and cell-of-origin type were prospectively analyzed by central pathology prior to random assignment and study treatment. Patients with ABC-DLBCL received lenalidomide oral 15 mg/d, days 1-14/21 plus standard R-CHOP21 versus placebo/R-CHOP21 for six cycles. The primary end point was progression-free survival (PFS) per independent central radiology review. RESULTS A total of 570 patients with ABC-DLBCL (n = 285 per arm) were stratified by International Prognostic Index score, age, and bulky disease, and randomly assigned to R2-CHOP or placebo/R-CHOP. Baseline demographics were similar between arms. Most patients completed six cycles of treatment: 74% R2-CHOP and 84% placebo/R-CHOP. The most common grade 3/4 adverse events for R2-CHOP versus placebo/R-CHOP were neutropenia (60% v 48%), anemia (22% v 14%), thrombocytopenia (17% v 11%), and leukopenia (14% v 15%). The primary end point of PFS was not met, with a hazard ratio of 0.85 (95% CI, 0.63 ...