The phase 3 ECHELON-3 study (NCT04404283) has demonstrated that the addition of brentuximab vedotin (BV) to lenalidomide and rituximab (R2) significantly improves survival outcomes in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Presented at the 2024 ASCO Annual Meeting, the study's interim data showed a 37% reduction in the risk of death with the BV triplet compared to the R2 and placebo regimen (HR, 0.629; 95% CI, 0.445-0.891; P = .0085).
At a median follow-up of 15.5 months for the BV triplet and 18.9 months for the R2 regimen, the median overall survival (OS) was 13.8 months and 8.5 months, respectively. The study also reported a 47% reduction in the risk of disease progression or death with the BV triplet, with median progression-free survival (PFS) increasing from 2.6 months in the R2 arm to 4.2 months in the BV arm.
The benefits of the BV triplet were consistent across all analyzed subgroups, regardless of CD30 expression, cell origin, or prior CAR T-cell therapy. This marks the first randomized, placebo-controlled phase 3 study to demonstrate an OS benefit in patients with relapsed/refractory DLBCL who have received more than two prior lines of systemic therapy.
Safety data indicated that the BV combination was well tolerated, with manageable adverse effects (AEs) and a safety profile consistent with the known profiles of each drug. The most common treatment-emergent adverse effects (TEAEs) in the BV group were neutropenia and thrombocytopenia, while neutropenia and anemia were most frequent in the R2 group.
This study highlights the potential of the BV triplet as a new treatment option for patients with relapsed/refractory DLBCL, particularly those unable to receive CAR T-cell therapy or a bispecific antibody, or those with disease relapse following such treatments.
