A Multidisciplinary Approach to Managing BTK Inhibitor Toxicity in Lymphoma and Chronic Lymphocytic Leukemia

Bruton tyrosine kinase inhibitors (BTKi) have transformed the treatment paradigm of patients with B-cell lymphomas. In recent years, studies of BTKi have demonstrated superior efficacy and an improved safety profile compared to cytotoxic therapy. Despite these improvements, patients still experience adverse events that can impact their quality of life and decrease their time on treatment. Because these drugs require continuous therapy to achieve optimal responses, minimizing drug holds or dose reductions is important to achieve best outcomes. It is important to identify and manage the adverse events that may appear during the use of BTKi to optimize the management of patients. Data from the phase 2 and phase 3 studies of the three approved BTKi ibrutinib, acalabrutinib, and zanubrutinib were reviewed to obtain information on relevant adverse events. Bibliographic research was performed to identify best practices and experiences on diagnosing and managing BTKi-related adverse events as well as prophylactic measures to reduce their impact. Diarrhea, bleeding, cytopenias, infections, headache, and fatigue were the most frequently observed adverse events with a frequency of more than 15% of patients. Other frequent events reported were arthralgia, skin manifestations, and cardiovascular events. Finally, rare events were compiled from individual case reports, such as hepatotoxicity, tumor lysis syndrome, progressive multifocal leukoencephalopathy, uveitis, and withdrawal syndrome. For each one, we provide an overview of the adverse event, considerations before starting BTKi therapy, potential drug-drug interactions and propose interventions to manage emerging toxicities. In addition, we describe the role of each specialist in the co-management of patients treated with BTKi. A multidisciplinary approach is recommended for treatment with BTKi, with different experts providing input into the strategies for assessment and prevention, as well as monitoring, diagnosing, and managing symptoms of BTKi-related adverse events. Additionally, communication with patients is essential for the shared decision-making process of treatment, recognizing symptoms related to adverse events, identifying existing risk factors, reporting concurrent medications, and monitoring treatment adherence.