Chronic Lymphocytic Leukemia Through the Spectrum: Frontline Therapy, Sequencing With Subsequent Therapy, and Treatment of Double-Refractory Patients

The rapid development of novel agents and combinations in chronic lymphocytic leukemia/small lymphocytic lymphoma has led to multiple options for frontline therapy and relapse, including continuous therapy and fixed duration regimens. The choice of therapy may be affected by the patient performance status, molecular abnormalities, potential side effects, logistics, patient expectations, and sequencing options in patients who will likely need more than one therapy in their lifetime. Current therapy options consist of several Bruton tyrosine kinase inhibitors (BTKis; covalent and noncovalent), one BCL-2 inhibitor (with others in development), and antibodies, with the possibility of single-agent therapy, doublets, or, less frequently, triplet therapy. In addition, treatment for double-refractory patients (refractory to both a BTKi and a BCL-2i) is available, but options are limited, so additional therapies for treatment in these high-risk patients are needed and in development.