FDA Approves Brentuximab Vedotin Combined With Lenalidomide and Rituximab for R/R Diffuse Large B-Cell Lymphoma
Brentuximab vedotin combined with lenalidomide and rituximab has been approved for patients ineligible for hematopoietic stem cell transplantation (HSCT) or CAR T-Cell therapy who have relapsed or refractory (R/R) diffuse large B-Cell lymphoma (DLBCL) on February 11, 2025 by the the US Food and Drug Administration (FDA) based on results from the phase 3 ECHELON-3 (NCT04404283) trial.
In this global, double-blind trial, researchers enrolled 230 patients with R/R DBCL treated with brentuximab vedotin (n= 112) or placebo (n= 118), in addition to lenalidomide and rituximab, and were randomized 1:1. The primary end point was overall survival (OS), secondary end points included objective response rate (ORR), progression free survival (PFS) and complete response (CR) rate.
Among included patients there was a median of 3 prior lines of therapy, of which 29% received CAR T-Cell therapy previously and 68% of patients were CD30 negative. The median treatment duration was longer for patients treated with brentuximab vedotin (3.6 months) than placebo (2.0 months). At a median follow-up of 16.4 months (range, 0.1 t0 31.5), the OS was higher among patients treated with brentuximab vedotin combined with lenalidomide and rituximab compared with placebo (13.8 months; 95% CI, 10.3 to18.8 vs 8.5 months; 95% CI, 5.4 to 11.7; hazard ratio [HR], 0.629; 95% CI, 0.445 to 0.891; P=0.0085).
Additionally, patients treated with brentuximab vedotin compared with patients treated with placebo showed higher rates of PFS (4.2 months; 95% CI, 2.9 to 7.1 vs 2.6 months; 95% CI, 1.4 to 3.1; HR, 0.527; 95% CI, 0.380 to 0.729; P<0.0001), ORR (64.3%; (95% CI, 54.7 to 73.1 vs 41.5%; 95% CI, 32.5 to 51.0; P=0.0006), and CR (40.2% vs 18.6%).
In terms of safety, reports of grade 3 or higher treatment-emergent adverse events were higher among the brentuximab vedotin group (88%) than the placebo group (77%). Compared with the brentuximab vedotin group, patients treated with placebo reported less instances of serious adverse events (60% vs 50%,) and grade 5 adverse events (12% vs 8%).
The most common adverse reactions at any grade for patients in the brentuximab vedotin group and the placebo group were neutropenia (46% vs 32%), anemia (29% vs 27%), and diarrhea (31% vs 23%). Peripheral neuropathy occurred more often in patients treated with brentuximab vedotin (31%) than placebo (24%).
The researchers concluded, “This triplet regimen represents a novel treatment option for [patients] with heavily pretreated R/R DLBCL.”
Sources:
FDA approves Brentuximab Vedotin with lenalidomide and Rituximab. U.S. Food and Drug Administration. Accessed February 12, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-brentuximab-vedotin-lenalidomide-and-rituximab-relapsed-or-refractory-large-b-cell?utm_medium=email&utm_source=govdelivery.
Results from the phase 3 echelon-3 study. Published online June 5, 2024. doi: 10.1200/JCO.2024.42.17_suppl.LBA7005.
