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The development of BTK inhibitors has revolutionized the management of CLL. Currently, there are 3 BTK inhibitors available to treat CLL: ibrutinib, acalabrutinib, and zanubrutinib (the latter not yet approved for this disease but included in the NCCN guidelines). In this review, we will elucidate our approach to the selection of BTK inhibitor and provide insight into the future of BTK directed therapy. This review utilizes data from published prospective trials, specifically RESONATE, RESONATE-2, ELEVATE-TN, ASCEND, ELEVATE-RR, and the ongoing FLAIR, SEQUOIA, and ALPINE trials. The choice of BTK inhibitor is guided by the setting (frontline vs relapsed) in conjunction with patient disease characteristics and comorbidities. In this review, we will elucidate our approach to the selection of BTK inhibitor and provide insight into the future of BTK directed therapy.

BTK inhibitor selection for chronic lymphocytic leukemia: which drug for which patient?