Considerations for the treatment of older adults with chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) primarily affects older adults, with a median age at diagnosis around 70 years. While targeted therapies have improved outcomes, treatment decisions in the elderly are complicated by comorbidities, fraility, and underrepresentation in clinical trials.

This review integrates geriatric oncology principles with therapeutic evidence to guide management of older adults with CLL. It summarizes frontline and relapsed/refractory strategies, drawing from landmark trials and real-world studies, and incorporates consensus on frailty assessment, polypharmacy, cardiovascular risk, and supportive care. Novel agents and treatment approaches are discussed in the context of functional status, patient preference, and quality of life, offering a practical age-adapted framework not addressed in prior reviews.

While modern therapies allow longer survival with improved tolerability, several controversies remain. One challenge is managing patients with borderline fitness - those not formally frail yet with significant comorbidities or organ dysfunction. Another is sequencing after intolerance or progression on both BTK and BCL2 inhibitors, where evidence is sparse. Emerging options such as non-covalent BTK inhibitors, bispecific antibodies, and CAR-T hold promise, but their role in older or frail patients is unclear. Future age-adapted trials and biomarker-driven strategies are needed to balance survival with quality of life.