TY - JOUR
T1 - ROBUST
T2 - 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
AU - ROBUST Trial Investigators
AU - Nowakowski, Grzegorz S.
AU - Chiappella, Annalisa
AU - Gascoyne, Randy D.
AU - Scott, David W.
AU - Zhang, Qingyuan
AU - Jurczak, Wojciech
AU - Özcan, Muhit
AU - Hong, Xiaonan
AU - Zhu, Jun
AU - Jin, Jie
AU - Belada, David
AU - Bergua, Juan Miguel
AU - Piazza, Francesco
AU - Mócikova, Heidi
AU - Molinari, Anna Lia
AU - Yoon, Dok Hyun
AU - Cavallo, Federica
AU - Tani, Monica
AU - Yamamoto, Kazuhito
AU - Izutsu, Koji
AU - Kato, Koji
AU - Czuczman, Myron
AU - Hersey, Sarah
AU - Kilcoyne, Adrian
AU - Russo, Jacqueline
AU - Hudak, Krista
AU - Zhang, Jingshan
AU - Wade, Steve
AU - Witzig, Thomas E.
AU - Vitolo, Umberto
N1 - Publisher Copyright:
Copyright © 2022 American Society of Clinical Oncology. All rights reserved.
PY - 2021/4/20
Y1 - 2021/4/20
N2 - 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 5 285 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 5 .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.
AB - 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 5 285 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 5 .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.
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U2 - 10.1200/JCO.20.01366
DO - 10.1200/JCO.20.01366
M3 - Article
C2 - 33621109
AN - SCOPUS:85104900537
SN - 0732-183X
VL - 39
SP - 1317
EP - 1328
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 12
ER -