Cardiovascular Toxicities of BTK Inhibitors in Chronic Lymphocytic Leukemia: JACC: CardioOncology State-of-the-Art Review

Cooper Quartermaine; Sanam M Ghazi; Aneeq Yasin; Farrukh T Awan; Michael Fradley; Tracy Wiczer; Sujay Kalathoor; Mussammat Ferdousi; Satyam Krishan; Alma Habib; Adnan Shaaban; Onaopepo Kola-Kehinde; Adam S Kittai; Kerry A Rogers; Michael Grever; Patrick Ruz; Seema Bhat; Tyler Dickerson; John C Byrd; Jennifer Woyach; Daniel Addison

doi:10.1016/j.jaccao.2023.09.002

Cardiovascular Toxicities of BTK Inhibitors in Chronic Lymphocytic Leukemia: JACC: CardioOncology State-of-the-Art Review

JACC CardioOncol. 2023 Oct 17;5(5):570-590. doi: 10.1016/j.jaccao.2023.09.002. eCollection 2023 Oct.

Authors

Cooper Quartermaine¹, Sanam M Ghazi¹, Aneeq Yasin¹, Farrukh T Awan², Michael Fradley³, Tracy Wiczer⁴, Sujay Kalathoor¹, Mussammat Ferdousi¹, Satyam Krishan⁵, Alma Habib⁶, Adnan Shaaban¹, Onaopepo Kola-Kehinde¹, Adam S Kittai⁶, Kerry A Rogers⁶, Michael Grever⁶, Patrick Ruz¹, Seema Bhat⁶, Tyler Dickerson⁴, John C Byrd⁷, Jennifer Woyach⁶, Daniel Addison^{1

8}

Affiliations

¹ Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus, Ohio, USA.
² Division of Hematology, UT-Southwestern Medical Center, Dallas, Texas, USA.
³ Cardio-Oncology Program, Division of Cardiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁴ Department of Pharmacy, James Cancer Hospital and Solove Research Institute, Columbus, Ohio, USA.
⁵ Department of Medicine, University of Oklahoma Medical Center, Oklahoma City, Oklahoma, USA.
⁶ Division of Hematology, The Ohio State University, Columbus, Ohio, USA.
⁷ Department of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
⁸ Division of Cancer Prevention and Control, The Ohio State University, Columbus, Ohio, USA.

Abstract

Over the past decade, the treatment landscape of chronic lymphocytic leukemia (CLL) has dramatically changed, shifting from cytotoxic chemotherapy to targeted therapies. Bruton's tyrosine kinase (BTK) inhibitors have revolutionized the treatment of CLL and are increasingly applied in many other malignancies. However, ibrutinib, the first BTK inhibitor approved, is associated with serious toxicities, including atrial fibrillation in up to 38% of patients, ventricular arrhythmias, and other cardiovascular toxicities. Emerging data suggest several newer BTK inhibitors (eg, acalabrutinib, zanubrutinib) are still associated with cardiotoxic risks. This review examines the current state of evidence, including incidence rates, risk factors, mechanisms, and management strategies of cardiovascular toxicities with BTK inhibitors and other CLL therapies. We specifically focus on atrial fibrillation, ventricular arrhythmias/sudden death, hypertension, heart failure, bleeding, and stroke. We also touch on other emerging BTK therapies (eg, pirtobrutinib). Finally, we highlight key unanswered questions and future directions of research.

Keywords: Bruton’s tyrosine kinase inhibitors; acalabrutinib; atrial fibrillation; cardio-oncology; ibrutinib; sudden death; zanubrutinib.

Publication types

Review