Considerations for the practical management of cardiovascular risk with Bruton's tyrosine kinase inhibitors for patients with chronic lymphocytic leukemia

Abstract

Background: Bruton's tyrosine kinase inhibitors (BTKis) are central to the medical management of chronic lymphocytic leukemia. However, accumulating data suggest an important association with cardiovascular (CV) adverse events (AEs), including arrhythmias, hypertension, and bleeding, in patients with chronic lymphocytic leukemia and other hematological malignancies treated with this therapeutic class. Data from comparative trials with BTKis suggest second-generation agents, for example, acalabrutinib and zanubrutinib, may be associated with fewer CV AEs than first-in-class BTKi ibrutinib.

Methods: PubMed and the proceedings of key hematology congresses were searched for relevant information using broad search terms, including chronic lymphocytic leukemia, BTKi, and toxicity.

Results: When managing patients with chronic lymphocytic leukemia, screening before and during treatment to assess CV risk is suggested to guide decision-making. Due to the increased toxicity with ibrutinib, the second-generation BTKis are now preferred (per the NCCN Clinical Practice Guidelines in Oncology [NCCN Guidelines]). For patients with a high CV risk, the decision between second-generation BTKi or a time-limited alternative, like venetoclax plus an anti-CD20 monoclonal antibody, should be made on an individual basis after patient consultation and consideration of the presenting characteristics of chronic lymphocytic leukemia in any given patient. The management of anticoagulant/antiplatelet medication during BTKi treatment requires specific attention, with coexistent medications being carefully assessed before starting a BTKi to reduce the risk of bleeding. For patients with a new-onset or worsening CV events during BTKi therapy, management may involve temporarily stopping the BTKi or switching to another class of therapy. To ensure the best outcomes, a collaborative care approach is essential, and some patients may need to be referred to a cardiologist/cardio-oncologist for specialist management.

Conclusion: Baseline and ongoing CV risk assessment, careful monitoring, management, and a multidisciplinary team approach are all critical to ensure optimal oncologic and CV outcomes for patients with chronic lymphocytic leukemia receiving BTKis.

Keywords: Bruton’s tyrosine kinase inhibitor; arrhythmia; cardiovascular; chronic lymphocytic leukemia; hemorrhage; hypertension.

Figure 1.

Management algorithm for patients with chronic lymphocytic leukemia by CV risk. Abbreviations: BTKi, Bruton tyrosine kinase inhibitor; CV, cardiovascular; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; iwCLL, International Workshop on Chronic Lymphocytic Leukemia; NSVT, non-sustained ventricular tachycardia; PVC, premature ventricular contractions; VT, ventricular tachycardia.