Triplet Therapies in Chronic Lymphocytic Leukemia.

Triplet therapy regimens, which we define as the combination of a BTK inhibitor (ibrutinib, acalabrutinib, zanubrutinib, or pirtobrutinib), BCL2 inhibitor (venetoclax or sonrotoclax), and a CD20 antibody (obinutuzumab), have been developed in chronic lymphocytic leukemia (CLL). Herein, we comprehensively review the available clinical data for triplet regimens in treatment-naïve CLL, including an evidence-based discussion of the role of TP53 aberrancy in patients receiving triplet therapies, and of retreatment options after frontline triplet therapy. We also review ongoing trials with potential to further define the role of triplet therapies in treatment-naïve CLL.