First-Line Therapy for Chronic Lymphocytic Leukemia: Bruton Tyrosine Kinase or BCL2 or Both?

Novel therapies largely have replaced chemoimmunotherapy as optimal first-line treatment of chronic lymphocytic leukemia (CLL). Approved novel therapies for CLL in the first-line setting include Bruton tyrosine kinase inhibitors, ibrutinib and acalabrutinib, and the BCL2 inhibitor venetoclax. Each of these novel agents has its own unique attributes and they have not been compared head to head in randomized trials. This review summarizes the pivotal trials that led to the approval of novel agents and compares the features of each agent to guide treatment decisions in treatment-naïve CLL. Ongoing studies investigating combinations of novel agents in the first-line setting also are discussed.