The promise of CAR T-cell therapy in aggressive B-cell lymphoma

Relapsed or refractory aggressive B-cell lymphoma has an extremely poor prognosis and efforts to develop novel therapies for these patients have failed for almost four decades until the advent of chimeric antigen receptor (CAR) T-cell therapy. Within the last one year, two anti-CD19 CAR T-cell therapy products, axicabtagene ciloleucel and tisagenlecleucel, were approved by the United States Food and Drug Administration for the treatment of relapsed or refractory large B-cell lymphoma after at least two lines of systemic therapy based on multicenter single-arm phase two clinical trials. Here, we will discuss the different components of the CAR construct and their mechanisms of action, the role of conditioning chemotherapy, the efficacy and toxicity observed with anti-CD19 CAR T-cell therapies in aggressive B-cell lymphomas, and emerging strategies to further improve the safety and efficacy of these highly promising approaches.