FDA approves brentuximab vedotin with lenalidomide and rituximab for relapsed or refractory large B-cell lymphoma

FDA approval (Feb 12, 2025)

The US Food and Drug Administration (FDA) approved brentuximab vedotin (Adcetris; Seagen Inc., a subsidiary of Pfizer) in combination with lenalidomide and a rituximab product for adult patients with relapsed or refractory large B-cell lymphoma (LBCL)—including DLBCL NOS, DLBCL arising from indolent lymphoma, or high-grade B-cell lymphoma—after ≥2 lines of systemic therapy, who are ineligible for autologous HSCT or CAR T-cell therapy.

Supporting evidence: ECHELON-3 (NCT04404283)

Approval was based on ECHELON-3, a randomized, double-blind, placebo-controlled trial (n=230) in relapsed/refractory LBCL patients ineligible for auto-HSCT or CAR T-cell therapy. Patients were randomized 1:1 to BV+lenalidomide+rituximab (BV+R2) vs placebo+R2, administered until progression or unacceptable toxicity.

Efficacy (major endpoint: OS):

• Median OS: 13.8 months (95% CI 10.3–18.8) with BV+R2 vs 8.5 months (95% CI 5.4–11.7) with placebo+R2 (HR 0.63, 95% CI 0.45–0.89; p=0.0085)
• Median PFS: 4.2 vs 2.6 months (HR 0.53; p<0.0001)
• ORR: 64.3% vs 41.5% (Lugano 2014)

Safety and dosing (selected)

Common adverse reactions (≥20%; excluding lab abnormalities) with BV+R2 included fatigue, diarrhea, peripheral neuropathy, rash, pneumonia, and COVID-19 infection. Peripheral neuropathy developed/worsened in 27%, leading to BV dose reduction in 6% and discontinuation in 4.5%.

Recommended BV dose: 1.2 mg/kg (max 120 mg) every 3 weeks with lenalidomide and rituximab until progression or unacceptable toxicity.