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  6. FDA approves brentuximab vedotin with lenalidomide and rituximab for relapsed or refractory large B-cell lymphoma
  1. Resources for Information | Approved Drugs

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

On February 11, 2025, the Food and Drug Administration 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 diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), DLBCL arising from indolent lymphoma, or high-grade B-cell lymphoma (HGBL), after two or more lines of systemic therapy who are ineligible for autologous hematopoietic stem cell transplantation (auto-HSCT) or CAR T-cell therapy.

Full prescribing information for Adcetris will be posted on Drugs@FDA. 

Efficacy and Safety

Approval was based on ECHELON-3 (NCT04404283), a randomized, double-blind, placebo-controlled trial enrolling 230 adult patients with relapsed or refractory LBCL who were ineligible to receive an auto-HSCT or CAR T-cell therapy. Patients were randomized 1:1 to receive brentuximab vedotin plus lenalidomide and rituximab (BV+R2) or placebo plus lenalidomide and rituximab (Pbo+R2) until disease progression or unacceptable toxicity.

The major efficacy outcome measure was overall survival (OS). Additional efficacy outcome measures included progression-free survival (PFS) and objective response rate (ORR) per 2014 Lugano Criteria. The trial demonstrated a statistically significant OS improvement with a median OS of 13.8 months (95% CI: 10.3, 18.8) in the BV+R2 arm and 8.5 months (95% CI: 5.4, 11.7) in the Pbo+R2 arm (Hazard ratio [HR] 0.63, 95% CI: 0.45, 0.89; p-value 0.0085). The trial also demonstrated a statistically significant improvement in PFS and ORR. Median PFS was 4.2 months (95% CI: 2.9, 7.1) with BV+R2 and 2.6 months (95% CI: 1.4, 3.1) with Pbo+R2 (HR 0.53, 95% CI: 0.38, 0.73; p-value <0.0001). The ORR was 64.3% (95% CI: 54.7, 73.1) and 41.5% (95% CI: 32.5, 51.0), respectively.

Adverse Reactions

The most common adverse reactions (≥20%), excluding laboratory abnormalities in the BV+R2 arm were fatigue, diarrhea, peripheral neuropathy, rash, pneumonia, and COVID-19 infection. Grade 3 to 4 laboratory abnormalities occurring in more than 10% were decreased neutrophils, decreased lymphocytes, decreased platelets, and decreased hemoglobin. Peripheral neuropathy developed or worsened in 27% of patients, was predominantly sensory, and led to brentuximab vedotin dose reduction in 6% and discontinuation in 4.5%. 

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

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

Follow the Oncology Center of Excellence on X: @FDAOncology. 
 

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