Balancing efficacy and toxicity of targeted agents currently used for the treatment of patients with chronic lymphocytic leukemia

n recent years, innovative mechanism-based drugs have enriched the therapeutic armamentarium for patients with chronic lymphocytic leukemia (CLL) and are widely used in the clinical practice. These small molecules targeting the B-cell receptor signaling pathway and the BCL-2 anti-apoptotic protein offer new chemo-free options to both unfit patients and high-risk patients who show a poor response to chemoimmunotherapy. Nonetheless, treatment with ibrutinib, idelalisib and venetoclax is associated with unique side effects. Awareness, prevention and the appropriate management of these specific toxicities are of crucial importance for a successful treatment. Areas covered: The purpose of this review is to discuss the most relevant studies on small molecules in CLL, with particular attention to the emerging toxicity profile of these agents and to the factors that should be considered to address the most appropriate treatment approach for each patient. Expert opinion: The increased knowledge on the biology of CLL has translated into the development of targeted agents that are highly effective and produce deep responses. Toxicities potentially associated with these agents should be known for an optimal management of CLL patients.