Even though the safety profile remained tolerable, treatment with lenalidomide plus R-CHOP did not improve progression-free survival compared with placebo plus R-CHOP for patients with activated B-cell-like subtype of DLBCL.
Research comparing the benefit of lenalidomide (Revlimid) added to standard rituximab (Rituxan) plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) against placebo plus R-CHOP for patients with activated B-cell–like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) failed to meet its primary end point, according to data published in the Journal of Clinical Oncology.
While the phase 3 ROBUST trial (NCT02285062) did not result in a statistically significant improvement in progression-free survival (PFS) via independent central radiology review, the lenalidomide plus R-CHOP combination maintained a tolerable safety profile for patients with ABC-type DLBCL.
“The global, phase III ROBUST study did not meet the primary end point for significantly improved progression-free survival with the lenalidomide/R-CHOP combination over control R-CHOP, although response rates were very high (91% overall response rate) in both study arms and median overall survival was not reached,” wrote the investigators. “The safety profile of lenalidomide plus R- CHOP was generally well tolerated, with no new safety signals with the addition of lenalidomide.”
The research data included 570 total patients with ABC-type DLBCL, with 285 patients each randomly assigned to either the lenalidomide plus R-CHOP arm or the placebo plus R-CHOP arm. Most of the patients completed all 6 treatment cycles (74% of lenalidomide patients versus 84% of placebo patients).
Common grade 3 or 4 adverse events for lenalidomide plus R-CHOP versus placebo plus R-CHOP included neutropenia (60% of patients versus 48% of patients), anemia (22% versus 14%), thrombocytopenia (17% versus 11%), and leukopenia (14% versus 15%).
PFS by independent central radiology review (HR, 0.85; 95% CI, 0.63-1.14; P = .29) and median PFS were not met. For patients with higher-risk disease, the PFS trends favored those in the lenalidomide group compared with the placebo group.
“Despite the lack of statistically significant efficacy benefit of lenalidomide with R-CHOP, these study results provide support for ongoing and future analyses to further evaluate the potential effect of pharmacokinetics or dosing, molecular classification, and mutational status in patients with diffuse large B-cell lymphoma,” wrote the investigators.
Prior to randomization and study treatment, the patient population had histology and cell-of-origin type prospectively analyzed by central pathology. The treatment cycles included oral lenalidomide at 15 mg on days 1 through 14 of every 21-day cycle or placebo plus R-CHOP for 6 cycles.
A potential limitation of the data according to the investigative team could be the median time from initial diagnosis to treatment initiation, which was recorded at 31 days. More, there was the potential for an additional delay due to the fact that most patients analyzed were referred from smaller community practices to treatment centers. These delays could have led to selection bias for patients with lower-risk disease.
“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,” concluded the investigators. “The meaning of (International Prognostic Index) 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. 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. February 23, 2021. doi:10.1200/JCO.20.01366