FDA Approves Brentuximab Vedotin Plus Lenalidomide, Rituximab for LBCL

The FDA has approved combination of brentuximab vedotin with lenalidomide and a rituximab product to treat relapsed or refractory large B-cell lymphoma (LBCL) in adults ineligible for autologous hematopoietic stem cell transplantation (AHSCT) or chimeric antigen receptor (CAR) T-cell therapy who have undergone at least two lines of systemic therapy. This new approval, announced by the FDA in a news release, includes diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma.

Brentuximab vedotin is marketed as Adcetris by Seagen Inc., a subsidiary of Pfizer Inc.

This new approval was based on data from the ECHELON-3 randomized, double-blind, placebo-controlled trial. In this trial, 230 adults with relapsed or refractory LBCL who were ineligible for AHSCT or CAR T-cell therapy were randomized 1:1 to receive either brentuximab vedotin plus lenalidomide and rituximab or placebo plus lenalidomide and rituximab.

In terms of efficacy, the brentuximab vedotin combination arm produced a median overall survival (OS) of 13.8 months, and the placebo combination arm, a median OS of 8.5 months, with a hazard ratio (HR) of .63 (P =.0085). The median progression-free survival (PFS) was 4.2 months in the brentuximab vedotin combination arm and 2.6 months in the placebo combination arm, with an HR of .53 (P<.0001). The objective response rate (ORR) was 64.3% in the brentuximab vedotin combination arm and 41.5% in the placebo combination arm.

Adverse reactions in the brentuximab vedotin combination arm that occurred with a frequency of 20% or greater were COVID-19 infection, diarrhea, fatigue, peripheral neuropathy, pneumonia, and rash. In this arm, 27% of patients experienced onset or worsening of peripheral neuropathy. The neuropathy was mostly sensory and led to brentuximab vedotin dose reduction in 6% of patients and discontinuation in 4.5%.

Grade 3 or 4 laboratory abnormalities that affected 10% or more of patients in the brentuximab vedotin combination arm were decreased hemoglobin, decreased lymphocytes, decreased neutrophils, and decreased platelets.

The FDA listed the recommended brentuximab vedotin dose to be 1.2 mg/kg up to a maximum of 120 mg in combination with lenalidomide and rituximab, to be administered every three weeks until the occurrence of unacceptable toxicity or disease progression.

Reference

FDA approves brentuximab vedotin with lenalidomide and rituximab for relapsed or refractory large B-cell lymphoma. FDA news release. FDA. February 11, 2025. Accessed February 18, 2025.