Polypharmacy in Chronic Lymphocytic Leukemia in the Era of Targeted Agents: A Medication Stewardship Perspective

Targeted therapies, including Bruton tyrosine kinase (BTK) inhibitors and venetoclax, have substantially improved clinical outcomes for patients with chronic lymphocytic leukemia (CLL). However, the increasing prevalence of polypharmacy in the predominantly older CLL population has emerged as a major challenge to the safe and effective delivery of these treatments. Multiple concomitant medications, particularly potentially inappropriate medications (PIMs), are associated with frailty, treatment-related toxicity, hospitalization, poor adherence, and inferior survival. These risks are further exacerbated by clinically significant drug-drug interactions with BTK inhibitors and venetoclax, as well as age-related pharmacokinetic changes. Integrating medication stewardship into routine CLL care-including medication reconciliation, interaction screening, adherence assessment, use of geriatric prescribing tools, and deprescribing of unnecessary or high-risk medications-may improve the safety and effectiveness of targeted therapies while reducing preventable treatment-related complications. Although current recommendations are largely extrapolated from geriatric oncology rather than CLL-specific studies, they may provide a practical framework for optimizing pharmacotherapy in this population.