Beyond Frailty Scores: Unmet Needs and Tailored Treatment Strategies in Patients With Chronic Lymphocytic Leukemia Aged ≥ 80 Years

ABSTRACT

Chronic lymphocytic leukemia (CLL) in patients aged ≥ 80 years represents a growing and clinically distinct population that remains underrepresented in clinical trials. Consequently, treatment decisions are often extrapolated from younger or “fit” cohorts, limiting their applicability in routine practice. While targeted therapies (i.e., novel agents such as Bruton tyrosine kinase inhibitors [BTKi] and BCL2 inhibitors) have substantially improved outcomes compared with chemoimmunotherapy, their use in very elderly patients is associated with higher rates of treatment discontinuation, dose reductions, and adverse events. Conventional frailty tools, largely based on comorbidity burden and renal function, fail to capture key age‐related vulnerabilities, such as functional decline, cognitive impairment, and reduced physiological reserve. Emerging data suggest that chronological age ≥ 80 years may identify a subgroup with specific clinical behavior and toxicity profiles that are insufficiently characterized by existing assessment models. In summary, elderly patients (aged ≥ 80 years) with CLL should be considered a distinct population requiring individualized, safety‐oriented therapeutic approaches. Dedicated clinical trials and adapted treatment algorithms are needed to optimize outcomes in this setting.