My Treatment Approach: Shared Decision-Making in CLL: Balancing Safety, Efficacy, and Patient Preference in CLL - Episode 8
ASH 2025 Data Watch: Anticipated Developments for the CLL Treatment Landscape
Panelists discuss how CLL treatment has evolved from universal single-agent BTKi use to personalized approaches based on patient risk factors like IGHV mutation status and TP53 mutations, with growing excitement about fixed-duration oral doublet therapies combining BTKis with venetoclax that show promising efficacy despite lower MRD rates compared with antibody-containing regimens, while addressing the management of BTKi class effects through dose-modification strategies and multidisciplinary care coordination, and anticipating future developments including BTK degraders that show excellent efficacy with improved safety profiles in highly refractory populations, bispecific antibodies for fixed-duration approaches, and results from the CLL17 trial comparing oral doublets to venetoclax-obinutuzumab that may further establish the role of time-limited combination therapies in transforming the treatment landscape.
This final segment focuses on anticipated developments in the chronic lymphocytic leukemia (CLL) treatment landscape, particularly looking ahead to the American Society of Hematology 2025 conference in December. The experts express significant excitement about Bruton tyrosine kinase (BTK) degraders, a novel class of drugs showing promising preliminary efficacy data in highly refractory patient populations who have progressed through multiple prior therapies. These agents work by degrading BTK protein rather than simply inhibiting it, potentially overcoming resistance mutations that can develop with traditional BTK inhibitors (BTKis). Early safety profiles appear favorable, with relatively low rates of the adverse events typically associated with BTKi therapy, making this class particularly promising for future development and combination strategies.
The discussion highlights several key clinical trials expected to provide important data, with particular emphasis on the CLL-17 study comparing ibrutinib monotherapy vs venetoclax plus obinutuzumab vs the ibrutinib-venetoclax combination. This trial represents the first true comparison of a fixed-duration oral doublet against the established venetoclax-based standard, which could significantly influence treatment paradigms. The experts anticipate this data will help determine whether fixed-duration approaches can definitively compete with continuous therapy strategies, building on earlier promising results from the FLAIR study’s minimal residual disease (MRD)-driven approach.
The experts also express interest in bispecific antibodies as an emerging therapeutic class for CLL, noting improved efficacy in relapsed/refractory settings with better toxicity profiles compared with earlier iterations. The key challenges for bispecifics involve optimizing safety profiles and developing delivery methods that can reach larger patient populations effectively. These novel immunotherapy approaches may offer additional fixed-duration treatment options while potentially enhancing immune system function in patients with CLL. The overall sentiment reflects optimism about the expanding therapeutic arsenal, with multiple new drug classes and combinations entering development to provide additional options for maintaining long-term disease control.
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