Chimeric Antigen Receptor T-Cell Therapy for Chronic Lymphocytic Leukemia: A Narrative Review

The treatment landscape for chronic lymphocytic leukemia (CLL) is changing rapidly. Novel targeted agents such as ibrutinib, venetoclax, and idelalisib have had a significant effect on first-line, relapsed/refractory, and high-risk disease. Despite these advances, there are continuous needs for new treatment options, especially for patients in whom these novel therapies fail or those who cannot tolerate these novel therapies. In 2011, Porter et al reported the first successful use of autologous chimeric antigen receptor T cells (CARTs) directed against cluster of differentiation (CD)19 in 3 refractory CLL patients. Several groups have since shown success with similar approaches in various settings of CLL, including failure of ibrutinib treatment and in patients who relapse after allogeneic stem cell transplantation. Although CD19-directed CART therapy holds great promise in CLL and other diseases, many challenges and questions remain including: optimization of the lymphodepletion regimen before CART infusion, optimal dosing of CART, a determination of the most effective CART product (T-cell subset[s]) as well as the optimal combinations and therapeutic sequences, and managing treatment-associated adverse events. Clinical trials addressing these challenges are in process. In this timely review, we analyze current state of CART therapy in CLL and attempt answering remaining questions.