The addition of lenalidomide to standard rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) was not found to improve outcomes for patients with the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL), according to the results of the randomized, phase 3 ROBUST trial published in the Journal of Clinical Oncology.
The trial (ClinicalTrials.gov Identifier: NCT02285062) included 570 adult patients with ABC-type DLBCL that was CD20-positive. Patients were enrolled between February 17, 2015, and August 3, 2017, from 257 study centers in 21 countries. Patients were randomly assigned treatment with either lenalidomide plus R-CHOP (R2-CHOP) or placebo plus R-CHOP.
The trial failed to meet its primary endpoint of statistically significant improved progression-free survival (PFS) for the R2-CHOP arm (hazard ratio [HR], 0.85; 95% CI, 0.63-1.14; P =.29). At 2 years, the PFS rate was similar between the R2-CHOP arm and the placebo plus R-CHOP arm (67% vs 64%), and no median PFS has been established for either arm.
Regarding secondary endpoints, no event-free survival improvement was seen for the R2-CHOP arm (HR, 1.04; 95% CI, 0.80-1.34; P =.73), and no difference in overall response rates was seen between arms (both, 91%).
An exploratory analysis indicated that patients with high-risk disease may have improved PFS with R2-CHOP. Specifically, a higher PFS rate was seen with R2-CHOP compared with placebo plus R-CHOP for patients with an International Prognostic Index (IPI) score of 3 or higher (59% vs 50%; P =.09), nonbulky disease (73% vs 66%; P =.05), and lower baseline creatinine clearance of 30 to 60 mL/min (69% vs 45%; P =.03).
“Despite the lack of benefit of lenalidomide with R-CHOP observed here, ongoing and future analyses will further evaluate the potential effect of pharmacokinetics or dosing, molecular classification, and mutational status,” the study authors wrote. “The meaning of IPI findings and why worse prognosis patients had better PFS when receiving lenalidomide remain to be further elucidated.”
Nowakowski GS, Chiappella A, Gascoyne RD, et al; on behalf of the ROBUST Trial Investigators. 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. J Clin Oncol. Published online February 23, 2021. doi:10.1200/JCO.20.01366