FDA

Adcetris combo therapy approved for relapsed/refractory large B-cell lymphoma

February 14, 2025

Brand name: Adcetris

Generic name: brentuximab

Manufacturer: Seagen, Inc., a subsidiary of Pfizer

Approval date: February 12, 2025

FDA approved Adcetris (brentuximab vedotin) in combination with lenalidomide and a rituximab product for adults 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 ≥2 lines of systemic therapy who are ineligible for autologous hematopoietic stem cell transplantation (auto-HSCT) or CAR T-cell therapy.

Efficacy

Approval was based on results from the ECHELON-3 trial (NCT04404283), which enrolled 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). The trial demonstrated a statistically significant OS improvement with a median OS of 13.8 months (95% confidence interval [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). ORR was 64.3% (95% CI, 54.7-73.1) and 41.5% (95% CI, 32.5-51.0), respectively.

Safety

The most common adverse reactions (≥20%), excluding lab abnormalities in the BV+R2 arm, were fatigue, diarrhea, peripheral neuropathy, rash, pneumonia, and COVID-19 infection. Grade 3 to 4 lab abnormalities occurring in >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%.

Recommended dose

The recommended brentuximab vedotin dosage is 1.2 mg/kg (max. 120 mg) in combination with lenalidomide and rituximab administered q3wks until disease progression or unacceptable toxicity.

Sources:

FDA approves brentuximab vedotin with lenalidomide and rituximab for relapsed or refractory large B-cell lymphoma. Food and Drug Administration. 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-brentuximab-vedotin-lenalidomide-and-rituximab-relapsed-or-refractory-large-b-cell

U.S. FDA Approves Pfizer’s ADCETRIS® Combination Regimen for the treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma. Pfizer. 2025. https://www.pfizer.com/news/press-release/press-release-detail/us-fda-approves-pfizers-adcetrisr-combination-regimen

Adcetris. Package insert. Pfizer. 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/125388Orig1s108lbl.pdf