My Treatment Approach: Shared Decision-Making in CLL: Balancing Safety, Efficacy, and Patient Preference in CLL - Episode 2
Identifying the Appropriate Patient With CLL for Continuous BTKi vs Fixed Duration BTKi + BCL-2i Regimens
Panelists discuss how treatment selection in CLL has evolved from universal single-agent BTKi use to a more personalized approach that considers patient-specific factors like IGHV mutation status, TP53 mutations, and 17p deletions, with growing excitement about emerging fixed-duration oral doublet therapies combining BTKis with BCL-2 inhibitors that may offer superior efficacy while reducing long-term toxicities and financial burden compared with continuous monotherapy approaches.
This segment explores the evolution of chronic lymphocytic leukemia (CLL) treatment approaches, focusing on the shift from continuous Bruton tyrosine kinase inhibitor (BTKi) monotherapy to fixed-duration combination regimens. The discussion reveals how clinical practice has adapted since 2016, when ibrutinib was the primary BTKi option used universally. Current practice patterns show variation among clinicians, with 1 expert using single-agent BTKis in approximately 40% to 50% of patients, while another uses BTK-based therapy about 30% of the time, reflecting the growing adoption of fixed-duration approaches, particularly following the introduction of venetoclax-based therapies.
Patient selection for different treatment approaches heavily depends on molecular characteristics and risk stratification. For patients with mutated IGHV status, venetoclax-based combinations (venetoclax plus obinutuzumab or rituximab) are often preferred due to excellent outcomes and deep minimal residual disease undetectability. Conversely, patients with high-risk features like 17p deletion or P53 mutations typically receive BTKis due to superior long-term results. For patients with unmutated IGHV, the choice becomes more nuanced, as they achieve longer remissions with BTKis but can benefit from fixed-duration approaches that allow treatment-free intervals.
The emergence of double oral fixed-duration combinations, particularly BTKi plus BCL-2 inhibitor regimens, represents a significant advancement in CLL treatment. Recent trial data from studies like CAPTIVATE and FLAIR have demonstrated, for the first time, superiority of double oral therapy over single-agent BTKis . This approach addresses practical challenges associated with infusion-based treatments while potentially reducing long-term toxicities and financial burden. The experts anticipate these combinations will become increasingly mainstream, though questions remain about their optimal use in high-risk populations such as those with TP53 alterations, where triple therapy or continuous treatment may still be necessary.
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