Seagen Inc., a Pfizer subsidiary, has received U.S. Food and Drug Administration (FDA) approval to use brentuximab vedotin (Adcetris) alongside rituximab and lenalidomide for treating adult patients with relapsed or refractory large B-cell lymphoma (LBCL). The FDA approval allows doctors to prescribe brentuximab vedotin to treat three different lymphoma subtypes, including diffuse large B-cell lymphoma (DLBCL) (not otherwise specified, NOS), indolent lymphoma of DLBCL origin and high-grade B-cell lymphoma (HGBL). The treatment is designed for patients who have undergone two previous systemic therapies but are ineligible for autologous hematopoietic stem cell transplantation (auto HSCT) or Chimeric antigen receptor (CAR) T-cell therapy.
FDA’s decision depended on findings from the decision following results from the ECHELON-3 trial (NCT04404283) involving 230 patients with LBCL who were unable to receive auto-HSCT or CAR T-cell therapy. Patients in this random sample received brentuximab vedotin combined with lenalidomide and rituximab through BV+R2 treatment or placebo treatment through Pbo+R2 in a defined 1:1 random allocation. The treatment protocol lasted until patients experienced disease progression or unacceptable treatment side effects.
The Primary endpoint of this study was overall survival (OS), the survival outcome used in this trial was overall survival (OS). In contrast, the secondary endpoints included progression-free survival (PFS) and objective response rate (ORR), assessed according to the 2014 Lugano criteria. The research showed that patients receiving BV+R2 had superior overall survival results with a median survival time of 13.8-month (95% confidence interval [CI]: 10.3, 18.8) when compared to Pbo+R2 participants who survived for 8.5 months on an average (95% confidence interval [CI]: 5.4, 11.7) (hazard ratio (HR) 0.63, 95% CI: 0.45, 0.89; p = 0.0085).
The study results exhibited remarkable advancement of both the PFS and ORR measurements. The patients who received BV+R2 achieved median progression-free survival results of 4.2 months (95% CI: 2.9–7.1) in the study, but patients in the Pbo+R2 group had a shorter median survival time of 2.6 months (95% CI: 1.4–3.1) (HR 0.53, 95% CI: 0.38–0.73; p < 0.0001). Patients under brentuximab vedotin with lenalidomide and rituximab had a 64.3% response rate (95% CI: 54.7–73.1), while the placebo group achieved 41.5% (95% CI: 32.5–51.0).
Patients who received BV+R2 therapy experienced fatigue along with diarrhea, peripheral neuropathy rash, pneumonia, and Coronavirus disease 2019 (COVID-19) infection as their most frequently reported adverse reactions (≥20%), excluding laboratory abnormalities. Treated participants experienced severe (Grade 3–4) lab abnormalities that affected neutrophils, lymphocytes, platelets, and hemoglobin levels at rates exceeding 10% among the study group.
The occurrence or worsening of peripheral neuropathy affecting the senses became evident in 27% of patients who received BV+R2 treatment. Approximately 6% of patients needed brentuximab vedotin dose adjustments, while 4.5% of patients stopped using the drug because of neuropathy complications.
Brentuximab vedotin received physician approval to administer at 1.2 mg/kg (up to 120 mg) every three weeks when used with lenalidomide and rituximab. Treatment continues until disease progression or unacceptable toxicity occurs. Brentuximab vedotin in combination therapy demonstrates great potential for LBCL patients with relapse or disease refractory state by improving their treatment response and survival outcomes.
References: U.S. Food and Drug Administration. FDA approves brentuximab vedotin with lenalidomide and rituximab for relapsed or refractory large B-cell lymphoma. Published February 12, 2025. Accessed February 13, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-brentuximab-vedotin-lenalidomide-and-rituximab-relapsed-or-refractory-large-b-cell
