Chronic Lymphocytic Leukemia — Proceedings from a Session Held in Conjunction with the 2026 ASCO Annual Meeting

Chronic Lymphocytic Leukemia (CLL) management has transitioned from traditional chemoimmunotherapy to targeted therapies, specifically BTK and BCL2 inhibitors. Continuous BTK inhibition remains a standard, though newer, more selective agents like acalabrutinib and zanabrutinib offer improved cardiovascular and safety profiles compared to ibrutinib. Fixed-duration regimens, such as venetoclax combined with obinutuzumab or BTK inhibitors, provide durable remissions and treatment-free intervals, particularly for patients prioritizing time off therapy. High-risk features like TP53 aberrations necessitate careful sequencing, often favoring zanabrutinib or pirtobrutinib. For double-refractory patients, CAR T-cell therapy, specifically lisocabtagene maraleucel, demonstrates significant efficacy, while emerging bispecific antibodies and BTK degraders offer promising alternatives for heavily pretreated populations. Clinical decision-making requires balancing efficacy, toxicity profiles, and patient-specific comorbidities, with a growing emphasis on managing treatment-emergent adverse events like tumor lysis syndrome and infections.