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A Patient-Centered Approach: Treatment Strategies for Progression and Intolerance in R/R CLL - Episode 3

Expert Perspectives: Sequencing Strategies after Acalabrutinib + Venetoclax +/- Obinutuzumab as First-Line Therapy in CLL

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Panelists discuss how sequencing therapies becomes challenging when using combination regimens like acalabrutinib-venetoclax in frontline treatment, requiring careful consideration of retreatment strategies and resistance mutation testing.

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    Future Treatment Considerations for Combination Therapy Relapses

    This segment explores theoretical treatment scenarios for patients who might receive acalabrutinib plus venetoclax combinations in frontline therapy, addressing the question of subsequent treatment options after exposure to multiple drug classes. The discussion acknowledges the current lack of retreatment data for this specific combination.

    Based on available evidence from the CAPTIVATE study, patients previously treated with ibrutinib plus venetoclax combinations have been successfully retreated with BTK inhibitor monotherapy, suggesting this approach might be feasible. However, experts emphasize the importance of testing for BTK resistance mutations, such as C481S and other gatekeeper mutations, before selecting subsequent BTK-based therapies.

    The conversation introduces the concept of "double-exposed" versus "double-refractory" patients, with implications for treatment selection. For younger patients with good performance status who relapse years after combination therapy, continued use of targeted therapies may provide better long-term outcomes than immediately transitioning to CAR-T or other cellular therapies, which could be reserved for truly refractory disease scenarios.

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