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 - Funding Information:
Supported by Celgene Corporation, a Bristol-Myers Squibb Company, Princeton, NJ. This study was conducted with the scientific support of the Fondazione Italiana Linfomi and the Mayo Clinc.
Funding Information:
Supported by Celgene Corporation, a Bristol-Myers Squibb Company, Princeton, NJ. This study was conducted with the scientific support of the Fondazione Italiana Linfomi and the Mayo Clinc. We would like to dedicate this work to the memory of Bertrand Coiffier after his untimely passing. Prof Coiffier was a foremost expert in the field and has our utmost respect for his significant contributions to the ROBUST study and to the field overall. Thank you to patients, families, caregivers, and investigators who participated in the ROBUST clinical study. Thank you to the Fondazione Italiana Linfomi (FIL) and Mayo Clinic for providing significant contributions and support for the study. Thank you to the international board of expert pathologists for providing histopathology review, and independent expert hematologist for clinical assessment and imaging review. Thank you to the data monitoring committee (DMC) that served as an independent expert advisory group to evaluate safety and efficacy throughout the study, including Bertrand Coiffier, MD (chair); Martin Dreyling MD; David Maloney MD, PhD; John Leonard MD; and Weichung Shih, PhD. The authors received editorial support in the preparation of this manuscript from Julie Kern, PhD, CMPP of Bio Connections LLC, funded by Celgene Corporation. The authors directed development of the manuscript and are fully responsible for all content and editorial decisions for this manuscript.
Funding Information:
We would like to dedicate this work to the memory of Bertrand Coiffier after his untimely passing. Prof Coiffier was a foremost expert in the field and has our utmost respect for his significant contributions to the ROBUST study and to the field overall. Thank you to patients, families, caregivers, and investigators who participated in the ROBUST clinical study. Thank you to the Fondazione Italiana Linfomi (FIL) and Mayo Clinic for providing significant contributions and support for the study. Thank you to the international board of expert pathologists for providing histopathology review, and independent expert hematologist for clinical assessment and imaging review. Thank you to the data monitoring committee (DMC) that served as an independent expert advisory group to evaluate safety and efficacy throughout the study, including Bertrand Coiffier, MD (chair); Martin Dreyling MD; David Maloney MD, PhD; John Leonard MD; and Weichung Shih, PhD. The authors received editorial support in the preparation of this manuscript from Julie Kern, PhD, CMPP of Bio Connections LLC, funded by Celgene Corporation. The authors directed development of the manuscript and are fully responsible for all content and editorial decisions for this manuscript.
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 -
