Clinical Advances in Hematology & OncologyHighlights in Chronic Lymphocytic Leukemia From the 66th ASH Annual Meeting and Exposition

This compilation presents key clinical trial results from ASH 2024 focusing on novel therapeutic approaches in chronic lymphocytic leukemia (CLL), including BTK inhibitors, BCL2 inhibitors, and combination therapies. The studies represent Phase 1-3 trials with varying levels of evidence, primarily investigating treatment outcomes in both treatment-naïve and relapsed/refractory settings.

Key Clinical Considerations:

• The AMPLIFY trial demonstrated superior PFS with acalabrutinib-venetoclax combinations vs. chemoimmunotherapy, with 3-year PFS rates of 76.5% (AV) and 83.1% (AVO) vs. 66.5% (FCR/BR)
• Pirtobrutinib-venetoclax-obinutuzumab achieved 100% uMRD4 in blood and 98% in bone marrow by cycle 13, with manageable safety profile and 100% PFS at median follow-up of 11.9 months
• Sonrotoclax plus zanubrutinib showed promising efficacy with 91% uMRD4 rates at week 48 (320mg cohort) and no progression events after 19.4 months follow-up
• BRUIN CLL-321 established pirtobrutinib’s superiority over idelalisib-rituximab/BR in BTK inhibitor-pretreated patients (median PFS 14.0 vs 8.7 months)
• Novel BTK degraders (NX-5948, BGB-16673) demonstrated activity in heavily pretreated patients, including those with resistance mutations, achieving ORRs of 75.5% and 77.6% respectively

HCN Medical Memo
These findings suggest a paradigm shift toward chemotherapy-free regimens with targeted combinations showing superior outcomes. The emergence of BTK degraders presents new options for resistant disease. Implementation requires careful patient selection, monitoring for specific toxicities, and consideration of treatment sequencing. Centers should develop protocols for managing unique adverse events associated with these novel therapies.

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