FDA Approves Adcetris Combo for DLBCL

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.

The approval is based on efficacy and safety data from the Phase III 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.

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. The most frequently reported treatment-emergent adverse events (TEAEs) Grade 3 or higher for the Adcetris versus placebo arms were: neutropenia (43% vs 28%), thrombocytopenia (25% vs 19%) and anemia (22% vs 21%). Peripheral sensory neuropathy was infrequent and low grade for each arm with Grade 3 events of 4% vs 0%.

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.

ECHELON-3 is an ongoing, randomized, double-blind, multicenter Phase III study evaluating Adcetris  plus lenalidomide and rituximab versus lenalidomide and rituximab plus placebo in adult patients with relapsed/refractory or transformed DLBCL, regardless of CD30 expression, who have received two or more prior lines of therapy and are ineligible for stem cell transplant (HSCT) or CAR-T therapy. The study also includes patients with hard-to-treat subtypes with poorer outcomes including double hit/triple hit lymphoma and patients with transformed disease. Patients may be ineligible to receive either HSCT or CAR-T therapy due to co-morbidities or financial, geographic, insurance, manufacturing issues. In this global study, 230 patients were randomized across North America, Europe and Asia-Pacific. The primary endpoint is OS in the intent to treat population, with key secondary endpoints of PFS and ORR as assessed by investigator. Other secondary endpoints include complete response rate, duration of response, safety and tolerability.

“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.”

“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 Dr. Roger Dansey, 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.”

See citation- Bartlett NL et al., Brentuximab Vedotin Combination for Relapsed Diffuse Large B-Cell Lymphoma. J Clin Oncol 2025,  0, JCO-24-02242 DOI:10.1200/JCO-24-02242