Dr Bhat on Using BTK Degraders and Bispecific Antibodies to Address Challenges With R/R CLL Management

"Novel therapies like bispecific antibodies and BTK degraders could address current challenges in relapsed/refractory CLL by offering newer mechanisms of action to target these resistant cells and potentially overcoming resistance to existing treatments."

Seema A. Bhat, MD, an associate professor in the Division of Hematology within the Department of Internal Medicine at The Ohio State University (OSU), as well as a hematologist-oncologist in the Leukemia and Hematologic Malignancies Program at the OSU Comprehensive Cancer Center—James, discussed how the ongoing development of novel bispecific antibodies and emerging class of BTK degraders could address current challenges in the management of relapsed/refractory chronic lymphocytic leukemia (CLL).

Novel therapies, such as bispecific antibodies and BTK degraders, use new mechanisms of action to overcome resistance in relapsed/refractory CLL, Bhat explained. These agents may enhance the immune system’s ability to recognize and eliminate malignant cells by targeting both a CLL-specific antigen, such as CD19 or CD20, and a T-cell receptor, such as CD3, Bhat noted. By bridging the immune system to the cancer cell, bispecific antibodies can trigger cytotoxic T-cell responses against the malignant clone, Bhat added.

Bispecific antibodies can also be combined with other targeted agents to further improve outcomes, Bhat said. She highlighted ongoing studies evaluating combinations like epcoritamab-bysp (Epkinly) plus venetoclax (Venclexta) and epcoritamab plus pirtobrutinib (Jaypirca) as promising investigational strategies. BTK degraders represent another novel class of agents with a distinct mechanism of action compared with conventional BTK inhibitors, Bhat observed. Unlike other inhibitors that block kinase activity, degraders promote direct degradation of the BTK protein, which may result in more profound tumor cell death, Bhat explained. Encouraging preclinical and early clinical data from BTK degrader trials were recently presented at the 2024 ASH Annual Meeting, underscoring the potential utility of these agents in overcoming disease resistance to prior BTK-directed therapies, Bhat concluded.