Bispecifics, BTK Inhibitors, and Immunotherapy Drive Lymphoma Advances
February 26, 2026
Key Points
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Epcoritamab plus rituximab and lenalidomide significantly improved response rates and progression-free survival (PFS) compared with standard therapy in relapsed/refractory (R/R) follicular lymphoma, according to data from the EPCORE FL-1 trial.
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In chronic lymphocytic leukemia (CLL), fixed-duration venetoclax plus obinutuzumab continues to compare favorably with continuous Bruton tyrosine kinase (BTK) inhibition, while frontline pirtobrutinib shows activity but is not yet practice-changing.
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Three-year follow-up data from the S1826 trial confirm superior PFS and tolerability with nivolumab-AVD (doxorubicin, vinblastine, dacarbazine) over brentuximab vedotin-AVD in advanced-stage Hodgkin lymphoma.
Data presented at the 2025 ASH Annual Meeting (ASH 2025) may influence practice across follicular lymphoma, CLL, and Hodgkin lymphoma. In a discussion with the Oncology Brothers, Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, Julie Vose, MD, MBA, of University of Nebraska Medical Center, shared insight on four key clinical trials: EPCORE FL-1, CLL-17, BRUIN CLL-313, and S1826.
BiTE Use in Lymphoma
The phase 3 EPCORE FL-1 trial evaluated epcoritamab, a subcutaneous bispecific T-cell engager antibody, in combination with rituximab and lenalidomide in patients with R/R follicular lymphoma who had received at least one prior therapy. Patients were randomized to the triplet regimen or standard therapy with rituximab plus lenalidomide. The experimental arm demonstrated superior overall and complete response rates, as well as improvement in PFS. Overall survival also favored the epcoritamab arm—an unexpectedly large benefit compared with standard therapy, Dr. Vose said.
Toxicities were manageable, with low-grade cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome. Dr. Vose emphasized the importance of infection monitoring, including checking immunoglobulin G levels in patients with recurrent infections and considering intravenous immunoglobulin replacement when appropriate.
CLL Trials to Watch
The CLL-17 study compared continuous BTK inhibitor–based therapy (ibrutinib) with fixed-duration venetoclax plus obinutuzumab or venetoclax–ibrutinib. With a median follow-up of approximately 34 months, the data remain immature, and longer observation is necessary to determine whether PFS differences emerge among subgroups, Dr. Vose said. While early signals are intriguing, she explained that more mature data are needed before discussing optimal frontline sequencing.
The global, phase 3 BRUIN CLL-313 trial evaluated the noncovalent BTK inhibitor pirtobrutinib in the frontline setting. The agent demonstrated superiority over bendamustine plus rituximab and was well tolerated, with a favorable safety profile, Dr. Vose said. However, she cautioned that while pirtobrutinib is highly active, particularly in the R/R setting, the available data are not yet practice-changing.
PFS Sustained in S1826 Trial
A three-year update from the S1826 trial comparing nivolumab-AVD with brentuximab vedotin-AVD in advanced-stage Hodgkin lymphoma was also presented at ASH 2025. The PFS advantage was greater with nivolumab-AVD compared with brentuximab vedotin-AVD (91% vs 82%, respectively), and the regimen showed improved tolerability. Based on these data, Dr. Vose feels that nivolumab-AVD should be strongly considered as a preferred option in advanced-stage disease.
Overall, these studies represent meaningful advances across lymphoma subtypes, with some findings positioned to change practice in select settings, the doctors said.