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
In the April 20, 2021 edition of Journal of Clinical Oncology, investigators report on the results of the ROBUST trial.
Patients with activated B-cell like diffuse large B-cell lymphoma, have historically shown inferior survival outcomes with standard R-CHOP therapy. The investigators developed a phase 3 clinical trial, adding the immunomodulatory agent, lenalidomide, the standard R-CHOP, R2-CHOP. This was based off a very successful phase 2 clinical trial, using R2-CHOP, previously untreated activated B-cell type diffuse large B-cell lymphoma.
Both histology and cell of origin type were analyzed prospectively prior to random assignment by central pathology center. Patients with activated B-cell subtype were treated with lenalidomide 50 mg daily orally, 14 out of 21 days plus standard R-CHOP21. Treatment was administered for 6 cycles. Progression free survival as the primary endpoint.
570 patients are randomized, 285 neutrophils. Patients were stratified by international prognostic index score, tumor bulkiness and patient age to either R-CHOP plus placebo or R2-CHOP. The majority of patients completed all 6 cycles, 74% of the treatment arm and 84% in the standard placebo arm. The most common grade 3 and 4 adverse events in the treatment arm, included neutropenia at 60%, anemia 22% and thrombocytopenia at 17%. This was in comparison to the standard arm of 40%, 40%, 11% respectively. The primary endpoint of progression free survival was not met. The hazard ratio 0.85, P = 0.29 with median progression free survival not reached in either arm. Progression free survival chance favoring R2-CHOP were seen in patients with high-risk disease.
The authors 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 end point of PFS in all patients, the safety profile of R2-CHOP was consistent with individual treatments with no new safety signals.”