The Food and Drug Administration (FDA) has approved Adcetris (brentuximab vedotin) in combination with Revlimid (lenalidomide) and Rituxan (rituximab) for the treatment of adults with relapsed or refractory large B-cell lymphoma (LBCL). This includes patients with diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), DLBCL arising from indolent lymphoma and high-grade B-cell lymphoma (HGBL), following two or more lines of systemic therapy and those who are ineligible for autologous hematopoietic stem cell transplantation (auto-HSCT) or CAR-T-cell therapy, according to the agency.
Glossary
Autologous hematopoietic stem cell transplantation (auto-HSCT): When a patient’s healthy blood-forming cells are collected before treatment, stored, then given back after treatment.
CAR-T cell therapy: When a patient’s T cells are collected, changed in a laboratory to attack cancer cells, grown in the laboratory and returned to the patient.
Overall survival (OS): The time a patient lives, regardless of disease status.
Progression-free survival: The time a patient lives without their disease spreading or worsening.
Objective response rate: Patients who responded partially or completely to treatment.
Peripheral neuropathy: A condition causing weakness, numbness or pain in the extremities.
This FDA approval was based on data from the phase 3 ECHELON-3 clinical trial which evaluated 230 patients with relapsed or refractory LBCL who were ineligible for auto-HSCT or CAR-T cell therapy. In the trial, Adcetris plus Revlimid and Rituxan (BV+R2) was compared with placebo plus Revlimid and Rituxan (Pbo+R2), resulting in a statistically significant improvement in overall survival (OS) with the investigative combination.
The median OS was 13.8 months in the BV+R2 arm and 8.5 months in the Pbo+R2 arm. Additionally, the median progression-free survival times were 4.2 months and 2.6 months, respectively, and the objective response rates were 64.3% and 41.5%.
“ECHELON-3 is one of the first randomized, placebo-controlled phase 3 studies to demonstrate an OS benefit in patients with relapsed/refractory DLBCL after two or more prior lines of systemic therapy,” said principal investigator Dr. Jeung-A Kim, College of Medicine, The Catholic University of Korea, in a news release issued in June 2024 by the drug’s manufacturer, Pfizer. “The clinically meaningful improvement in survival demonstrates the potential benefit of this Adcetris regimen in relapsed/refractory DLBCL, particularly for patients whose disease has progressed after CAR-T therapy or bispecific antibody treatment or individuals who are not able to receive these treatments.”
The most common side effects experienced by at least 20% of patients, excluding laboratory abnormalities, in the BV+R2 arm were fatigue, diarrhea, peripheral neuropathy, rash, pneumonia and COVID-19 infection, while grade 3 (severe) to 4 (life-threatening) laboratory abnormalities experienced by more than 10% of patients included decreased neutrophils, decreased lymphocytes, decreased platelets and decreased hemoglobin. The agency reported that peripheral neuropathy developed or worsened in 27% of patients, was predominantly sensory and led to Adcetris dose reduction in 6% of patients and discontinuation in 4.5%.
