CAR T‐cells: Driving in the Fast Lane

Chimeric antigen receptor (CAR) T-cell therapy as a treatment This remarkable efficacy of CD19-directed CAR T-cells in modality has accelerated in a remarkable fashion in recent years and is now a standard of care for treating patients with relapsed and refractory diffuse large B-cell lymphoma (DLBCL) and relapsed pediatric and adolescent B-cell acute lymphoblastic leukemia (B-ALL). This dramatic progress in the CAR T-cell field has been summarized in recent publications in HemaSphere. These articles have comprehensively reviewed the substantial successes of CAR T-cell treatment as well as the potential for the future, but have also highlighted toxicity and future challenges. The success of CAR T-cell therapy has not only been due to technological advances allowing for the manufacture of these cells; treatment with CAR T-cells has been effective in populations of patients where other treatments have been unsuccessful. In DLBCL, patients with refractory disease who have a very poor prognosis were the initial cohort to be treated with CAR T-cells. In a prior analysis of 861 patients treated with standard chemotherapy, the objective response rate to the next line of standard therapy was only 26% with a complete response (CR) rate of 7%. The median survival for patients was only 6.3 months with only 20% of patients still alive at 2 years. It was in this very poor prognosis group of patients that CAR T-cell therapy showed very high and durable responses. Similarly, pediatric and adolescent patients with relapsed or refractory ALL have a very poor outcome. In a review of 313 patients, CR rates for patients in second or subsequent relapse were only 40% and the disease-free survival for patients in CR2 and CR3 was only 27% and 15%, respectively. It was these challenging subpopulations of ALL patients who received CAR T-cells and in whom substantial and durable responses were seen.