Accelerating chimeric antigen receptor therapy in chronic lymphocytic leukemia: The development and challenges of chimeric antigen receptor T-cell therapy for chronic lymphocytic leukemia

Studies of chimeric antigen receptor (CAR) T-cell therapy in chronic lymphocytic leukemia (CLL) have demonstrated the potential to produce deep remissions-and possibly cures-in some patients with heavily pretreated, high-risk, relapsed, and refractory disease. Unfortunately, most clinical trials of CAR T cells in CLL report complete responses only in the minority of patients, although recent studies have begun to elucidate the factors most predictive of response. These studies have suggested strategies for optimizing CAR T-cell fitness as well as the pre-existing host immune response, approaches that will likely lead to improvements in the efficacy of CAR T cells in CLL. Treating patients earlier in the course of their disease or using combination therapies with CAR T cells may further enhance efficacy. In this review, we summarize the existing literature on CAR T cell therapy in CLL, discuss mechanisms of response and resistance, and describe challenges facing the field.