Monitoring and Managing BTK Inhibitor Treatment-Related Adverse Events in Clinical Practice

Frontiers in Oncology

Susan M. O’Brien¹  Jennifer R. Brown²  Richard R. Furman³  William G. Wierda⁴  Paolo Ghia⁵  Jeff P. Sharman⁶  John C. Byrd⁷ 

[1] Chao Family Comprehensive Cancer Center, University of California, Orange, CA, United States;Chronic Lymphocytic Leukemia (CLL) Center, Dana-Farber Cancer Institute, Boston, MA, United States;Chronic Lymphocytic Leukemia (CLL) Research Center, New York-Presbyterian/Weill Cornell Medical Center, New York, NY, United States;Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, United States;Division of Experimental Oncology, Università Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milano, Italy;Division of Hematology Research for US Oncology, Willamette Valley Cancer Institute/US Oncology, Eugene, OR, United States;James Cancer Hospital and Solove Research Institute, The Ohio State University Comprehensive Cancer Center and Division of Hematology, Columbus, OH, United States;

关键词: acalabrutinib;    adverse events;    Bruton tyrosine kinase inhibitor;    chronic lymphocytic leukemia;    ibrutinib;   

DOI  :  10.3389/fonc.2021.720704

来源: DOAJ

【 摘 要 】

Bruton tyrosine kinase (BTK) inhibitors represent an important therapeutic advancement for B cell malignancies. Ibrutinib, the first-in-class BTK inhibitor, is approved by the US FDA to treat patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), and mantle cell lymphoma (MCL; after ≥1 prior therapy); and by the European Medicines Agency (EMA) for adult patients with relapsed/refractory (R/R) MCL and patients with CLL. Ibrutinib treatment can be limited by adverse events (AEs) including atrial fibrillation, arthralgias, rash, diarrhea, and bleeding events, leading to drug discontinuation in 4%–26% of patients. Acalabrutinib, a second-generation BTK inhibitor, is approved by the FDA to treat adult patients with CLL/SLL or MCL (relapsed after 1 prior therapy); and by the EMA to treat adult patients with CLL or R/R MCL. The most common AE associated with acalabrutinib is headache of limited duration, which occurs in 22%–51% of patients, and is mainly grade 1–2 in severity, with only 1% of patients experiencing grade ≥3 headache. Furthermore, acalabrutinib is associated with a low incidence of atrial fibrillation. Zanubrutinib, a selective next-generation covalent BTK inhibitor, is approved by the FDA to treat adult patients with MCL who have received ≥1 prior therapy, and is under investigation for the treatment of patients with CLL. In the phase 3 SEQUOIA trial in patients with CLL, the most common grade ≥3 AEs were neutropenia/neutrophil count decreased and infections. This review provides an overview of BTK inhibitor-related AEs in patients with CLL, and strategies for their management.

【 授权许可】

Unknown