Too frail or not too frail? Prognosis and treatment options in older CLL patients

Chronic lymphocytic leukemia (CLL) is a disease that primarily affects older patients, with a median age at diagnosis of 72 years. Older patients, in this review defined as 80 years or older, comprise about 20% of patients with CLL yet remain underrepresented in clinical trials. Available results indicate that with advancing age, treatment efficacy decreases with regard to progression-free survival, mostly due to an impaired tolerability, i.e., higher frequency and severity of adverse events, leading to weaker treatment adherence. This underscores the fact that even with the advent of novel agents, older patients remain a distinct patient group for which results from younger patients cannot reliably be superimposed. Older patients not only exhibit higher rates of comorbidities, especially of cardiovascular nature, but also more often show features of a symptom complex, associated with impaired physiological reserve to stressors and termed “frailty.” Frailty itself has an overlap with symptoms of hematological diseases but was shown to independently impact survival in hematological malignancies. Data on treatment in this at-risk patient group are scarce. Initial results from prospective clinical trials, such as the CLL-Frail trial by the German CLL Study Group or retrospective analyses of venetoclax + obinutuzumab treatment, show that targeted treatment is highly effective in this age group and might overcome fitness impairments. However, shared decision-making remains vital so as to always align these treatment prospects with individual patient-specific outlooks and goals. © The Author(s) 2025.