As reported in the Journal of Clinical Oncology by Grzegorz S. Nowakowski, MD, and colleagues, the phase III ROBUST trial showed that the addition of lenalidomide to R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone; R2-CHOP) did not significantly improve progression-free survival in previously untreated activated B-cell–like (ABC)-type diffuse large B-cell lymphoma (DLBCL).

Grzegorz S. Nowakowski, MD

Study Details

In the double-blind trial, 570 patients from sites in 21 countries were randomly assigned between February 2015 and August 2017 to receive lenalidomide at 15 mg (n = 285) or placebo (n = 285) on days 1 to 14 of 21-day cycles plus standard R-CHOP in 21-day cycles for six cycles. The primary endpoint was progression-free survival on independent central radiology review.

Progression-Free Survival

Median follow-up for all surviving patients was 27.1 months (range = 0–47 months). The primary endpoint of progression-free survival was not met, with a hazard ratio (HR) for the R2-CHOP vs R-CHOP group of 0.85 (95% confidence interval [CI] = 0.63–1.14, P =.29). Median progression-free survival was not reached in either group, with estimated 2-year rates of 67% vs 64%. 

Exploratory subgroup analyses suggested trends in 2-year progression-free survival favoring the R2-CHOP group among 329 patients with International Prognostic Index risk score ≥ 3 (59% vs 50%, P = .09), 374 patients with nonbulky disease (73% vs 66%, P = .05), and 80 patients with lower baseline creatinine clearance (30 to < 60 mL/min; 69% vs 45%, P = .03).

The key secondary efficacy endpoint of event-free survival was not met (HR = 1.04, 95% CI = 0.80–1.34, P = .73). Median event-free survival was not reached in either group, with estimated 2-year rates of 59% vs 61%. Overall survival data were not mature; median overall survival was not reached in either group, with estimated 2-year rates of 79% vs 80%. Objective response was observed in 91% vs 91% of patients, with complete response in 69% vs 65%. Median duration of response was not reached in either group.

Adverse Events

Grade 3 to 4 adverse events occurred in 78% of patients in the R2-CHOP group vs 71% of the R-CHOP group, with the most common in the R2-CHOP group being neutropenia (60% vs 48%), anemia (22% vs 14%), thrombocytopenia (17% vs 11%), and leukopenia (14% vs 15%). Serious adverse events were reported in 37% vs 31% of patients. Adverse events led to discontinuation of treatment in 17% vs 11% of patients, with the most common being neutropenia (8% vs 5%).

The investigators concluded, “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 endpoint of progression-free survival in all patients, the safety profile of R2-CHOP was consistent with individual treatments with no new safety signals.”

Dr. Nowakowski, of the Division of Hematology, Mayo Clinic, Rochester, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was funded by Celgene Corporation, a Bristol Myers Squibb Company. For full disclosures of the study authors, visit ascopubs.org.