Chronic lymphocytic leukemia: criteria for first-line therapeutic choice-an opinion paper

Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in the Western World, with 70% of patients asymptomatic at diagnosis. Treatment initiation follows specific criteria, including evidence of active disease. Recent advancements in Bruton's tyrosine kinase (BTK) inhibitors like acalabrutinib and zanubrutinib offer improved efficacy and safety profiles, impacting treatment choice for all patients namely elderly patients with comorbidities. In this opinion paper, a panel of experienced hematologists sought to establish criteria for selecting therapy in CLL and examine how the introduction of second-generation BTK inhibitors will influence these criteria. Experts recommend prioritizing criteria for CLL treatment selection: cytogenetics, comorbidities, age, socioeconomic factors, and patient preferences. Assessing IGHV mutational status, del(17p), and TP53 mutation is crucial for predicting treatment response, with repeat assessments for the latter before each retreatment. Comorbidities and patient well-being, including literacy, adherence, and living conditions, should be considered. Age alone should not limit treatment options; a holistic approach is needed, including geriatric evaluation. Patient involvement in treatment decisions is vital, considering treatment comprehension, toxicity, and individual preferences. New-generation BTK inhibitors offer improved efficacy and lower toxicity, particularly beneficial for patients with multiple comorbidities, including cardiovascular conditions. In conclusion, in the era of targeted therapies, treating elderly and multimorbid CLL patients requires balancing safety and efficacy, considering quality of life and life expectancy. Targeted therapy is preferred for most patients, with geriatric assessment pivotal for treatment decisions. Second-generation drugs aim to improve outcomes both in efficacy and safety, advocating for a patient-centered approach in clinical studies.