Blood and Lymphatic Cancer: Targets and Therapy (Jul 2022)
Use of BTK Inhibitors in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL): A Practical Guidance
Abstract
Frédérique St-Pierre,1 Shuo Ma1,2 1Department of Medicine, Division of Hematology/Oncology and the Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA; 2Department of Medicine, Division of Hematology/Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USACorrespondence: Shuo Ma, Division of Hematology-Oncology, Department of Medicine, Feinberg School of Medicine and the Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Tel +1 312-695-0990, Email [email protected]: The treatment landscape of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has changed significantly since the development of oral Bruton’s tyrosine kinase (BTK) inhibitors. While chemoimmunotherapy was previously the standard of care for first-line treatment, BTK inhibitors have proven to be a highly effective and safe therapeutic option for CLL/SLL, and now constitute one of the preferred first-line options. Ibrutinib, the first approved covalent BTK inhibitor in CLL/SLL, has the most long-term data supporting its efficacy in CLL/SLL treatment although is associated with increased risk of cardiovascular and hemorrhage adverse events due to off-target kinase inhibition. The second-generation covalent BTK inhibitors, including acalabrutinib and zanubrutinib, are more selective to BTK with less off-target effects. Resistance to covalent BTK inhibitors may emerge over time due to mutations in BTK and downstream kinases. Novel non-covalent BTK inhibitors currently being studied are showing promising activities to overcome such resistance. In this review, we discuss the role of BTK inhibitors in treatment of CLL/SLL, review the data that led to approval of BTK inhibitors in CLL/SLL, outline the toxicity profile of each approved BTK inhibitor and management, and give practical guidance on how to select the most appropriate agent for treatment.Keywords: Bruton’s tyrosine kinase inhibitor, chronic lymphocytic leukemia/small lymphocytic lymphoma, ibrutinib, acalabrutinib, zanubrutinib
