USFDA approves Pfizer Adcetris combination regimen for Relapsed/Refractory Diffuse Large B-Cell Lymphoma
New York: Pfizer Inc. has announced that the U.S. Food and Drug Administration (FDA) has approved the supplemental Biologics License Application (sBLA) for ADCETRIS (brentuximab vedotin) in combination with lenalidomide and a rituximab product for the treatment of 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 not eligible for autologous hematopoietic stem cell transplantation (auto-HSCT) or chimeric antigen receptor (CAR) T-cell therapy.
“Each year, more than 3,500 patients in the U.S. with this aggressive form of non-Hodgkin lymphoma experience treatment failure or relapse after two prior lines of therapy,” said Roger Dansey, M.D., Chief Oncology Officer, Pfizer. “The approval further reinforces the important role of ADCETRIS as an existing standard of care with overall survival improvement shown for certain types of lymphomas, and now allows physicians to have an option beyond chemotherapy or CAR-Ts for patients with relapsed/refractory large B-cell lymphoma.”
The approval is based on efficacy and safety data from the Phase 3 ECHELON-3 study, which demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) in patients with relapsed/refractory DLBCL who received ADCETRIS in combination with lenalidomide and rituximab. The study included patients who were heavily pre-treated, some of whom had received prior CAR-T therapy, and survival benefit was observed irrespective of CD30 expression.
“Patients with large B-cell lymphoma can face a challenging journey, with too many patients enduring multiple rounds of chemotherapy and even CAR-T therapy with limited success,” said principal investigator Dr. Craig Portell, Associate Professor, University of Virginia. “For patients who have previously faced setbacks with other therapies, ADCETRIS provides a new therapeutic option with outpatient administration and proven safety and efficacy.”
LBCL is a type of non-Hodgkin lymphoma (NHL), that affects immune cells called B lymphocytes, a type of white blood cell crucial to the body's immune system. DLBCL is the most common, aggressive and difficult-to-treat form of the disease. More than 25,000 cases of DLBCL are diagnosed each year in the United States, accounting for more than 25% of all lymphoma cases. Up to 40% of patients relapse or have refractory disease after frontline treatment, and more than 3,500 patients a year fail two prior lines of therapy and require third-line therapy. Despite recent treatment advances including bispecifics and CAR-T therapy, there remains a high unmet need for patients who are not eligible for these treatments or whose disease returns following treatment with these therapies.
The ECHELON-3 study showed that the ADCETRIS combination reduced patients’ risk of death by 37% compared to placebo in combination with lenalidomide and rituximab (HR 0.63 [95% CI: 0.445-0.891] p=0.0085). The OS benefit was consistent across levels of CD30 expression. Positive outcomes were also observed in key secondary endpoints, including overall response rate (ORR) and progression-free survival (PFS).
The safety profile of ADCETRIS in ECHELON-3 was consistent with its known safety profile as presented in the U.S. prescribing information.
Detailed data from ECHELON-3 were published in JCO Oncology Practice on January 7, 2025 and presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.
