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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
GS. Nowakowski, A. Chiappella, RD. Gascoyne, DW. Scott, Q. Zhang, W. Jurczak, M. Özcan, X. Hong, J. Zhu, J. Jin, D. Belada, JM. Bergua, F. Piazza, H. Mócikova, AL. Molinari, DH. Yoon, F. Cavallo, M. Tani, K. Yamamoto, K. Izutsu, K. Kato, M....
Language English Country United States
Document type Clinical Trial, Phase III, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
NLK
Free Medical Journals
from 2004 to 1 year ago
Open Access Digital Library
from 1999-01-01
PubMed
33621109
DOI
10.1200/jco.20.01366
Knihovny.cz E-resources
- MeSH
- Cyclophosphamide administration & dosage adverse effects MeSH
- Lymphoma, Large B-Cell, Diffuse drug therapy mortality MeSH
- Adult MeSH
- Doxorubicin administration & dosage adverse effects MeSH
- Lenalidomide administration & dosage adverse effects MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Prednisone administration & dosage adverse effects MeSH
- Antineoplastic Combined Chemotherapy Protocols administration & dosage adverse effects MeSH
- Rituximab administration & dosage adverse effects MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Vincristine administration & dosage adverse effects MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Comparative Study MeSH
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.
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 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 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
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
References provided by Crossref.org
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