[First-line treatment of elderly patients with CLL: An innovative, chemo-free approach].

Nowadays, a wide range of targeted therapies are available for the treatment of chronic lymphocytic leukemia, offering superior efficacy and a longer-lasting responses compared to chemoimmunotherapy in both first- and second-line settings. Owing to the favorable tolerability of novel targeted agents, genetic factors have superseded age and fitness as key determinants in the selection of first-line therapy. Currently, high-risk genetic features include del(17p13) or TP53 mutations, complex karyotype (≥3 chromosomal aberrations), and unmutated IGHV status. Initial risk stratification focuses on detecting del(17p13)/TP53 mutations and assessing karyotype. This new strategy, along with the improved tolerability of these agents, offers particular benefit to older and frail patients, with dosing tailored to comorbidities and concomitant therapies.Given the heterogeneity in older patients' health status, geriatric assessments (e.g., CIRS, FRAIL score) are additional key for individualized therapy decisions and adverse events influence therapy choice (e.g. cardiovascular risk with BTK inhibitors. Beyond clinical factors, patient preferences-such as opting for continuous (e.g., BTK inhibitor monotherapy) versus time-limited therapy (e.g., venetoclax plus obinutuzumab or ibrutinib plus venetoclax)-and treatment tolerability are decisive.