On 11 February 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 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 haematopoietic stem cell transplantation (auto-HSCT) or CAR T-cell therapy.
Approval was based on ECHELON-3 (NCT04404283), a randomised, double-blind, placebo-controlled study enrolling 230 adult patients with relapsed or refractory LBCL who were ineligible to receive an auto-HSCT or CAR T-cell therapy. Patients were randomised 1:1 to receive brentuximab vedotin plus lenalidomide and rituximab (BV plus R2) or placebo plus lenalidomide and rituximab (Pbo plus 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 study 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 plus R2 arm and 8.5 months (95% CI 5.4, 11.7) in the Pbo plus R2 arm (hazard ratio [HR] 0.63, 95% CI 0.45, 0.89; p-value = 0.0085). The study also demonstrated a statistically significant improvement in PFS and ORR. Median PFS was 4.2 months (95% CI 2.9, 7.1) with BV plus R2 and 2.6 months (95% CI 1.4, 3.1) with Pbo plus 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.
The most common adverse reactions (≥ 20%), excluding laboratory abnormalities in the BV plus R2 arm were fatigue, diarrhoea, peripheral neuropathy, rash, pneumonia, and COVID19 infection. Grade 3 to 4 laboratory abnormalities occurring in more than 10% were decreased neutrophils, decreased lymphocytes, decreased platelets, and decreased haemoglobin. Peripheral neuropathy developed or worsened in 27% of patients, was predominantly sensory, and led to BV dose reduction in 6% and discontinuation in 4.5%.
The recommended BV 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.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact FDA’s Oncology Center of Excellence Project Facilitate.