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 to 1.14) and P = .29; median PFS has not been reached for either arm. PFS trends favoring R2-CHOP over placebo/R-CHOP were seen in patients with higher-risk disease. CONCLUSION: ROBUST is the first DLBCL phase III study to integrate biomarker-driven identification of eligible ABC patients. Although the ROBUST trial did not meet the primary end point of PFS in all patients, the safety profile of R2-CHOP was consistent with individual treatments with no new safety signals.

4th Department of Internal Medicine Hematology Charles University Hospital and Faculty of Medicine Hradec Králové Czech Republic

AOU Città della Salute e della Scienza di Torino Turin Italy

Beijing Cancer Hospital Beijing China

Cancer Hospital Fudan University Shanghai China

Centre for Lymphoid Cancer British Columbia Cancer Vancouver British Columbia Canada

Clinical Research and Development Celgene Corporation Summit NJ

Department of Hematology and Cell Therapy Aichi Cancer Center Hospital Nagoya Japan

Department of Hematology Ankara University Ankara Turkey

Department of Internal Medicine and Haematology Faculty Hospital Kralovske Vinohrady Prague Czech Republic

Department of Medicine and Biosystemic Science Kyushu University Faculty of Medicine Fukuoka City Japan

Department of Oncology Asan Medical Center University of Ulsan College of Medicine Seoul South Korea

Department of Statistical Programming Celgene Corporation Overland Park KS

Division of Hematology A O U Città della Salute e della Scienza Hospital and University Torino Italy

Division of Hematology Department of Medicine University of Padova and Azienda Ospedaliera di Padova Padova Italy

Division of Hematology Mayo Clinic Rochester MN

Harbin Medical University Cancer Hospital Harbin Heilongjiang China

Maria Sklodowska Curie Institute Oncology Centre Cracow Poland

National Cancer Center Hospital Tokyo Japan

Servicio de Hematologia Hospital Universitario San Pedro de Alcántara Cáceres Spain

The 1st Affiliated Hospital of Medical School of Zhejiang University 1st Hospital of Zhejiang Province Hangzhou Zhejiang China

Translational Development Precision Medicine and Companion Diagnostics Celgene Corporation Summit NJ

U O Ematologia Dipartimento Oncologia e Ematologia Ospedale Santa Maria delle Croci Ravenna Italy

UO Ematologia Ospedale Degli Infermi Rimini Italy

J Clin Oncol. 2021 Apr 20;39(12):1314-1316. doi: 10.1200/JCO.20.03531. PubMed

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ClinicalTrials.gov
NCT02285062

EudraCT
2013-004054-21