Chimeric Antigen Receptor Therapy in Lymphoma

Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment for chemorefractory B-cell lymphoma. Pivotal phase II clinical trials exploring autologous anti-CD19 CAR T cells has resulted in approved indications for relapsed or refractory diffuse large B-cell lymphoma, transformed lymphoma, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, mantle cell lymphoma, and follicular lymphoma as a result of transformative response rates and overall survival. With three approved autologous CAR T-cell therapies in the management of aggressive B-cell lymphoma and no randomized study to inform selection of CAR T-cell construct, we aim to highlight the differences in the study populations and trial designs that may have impacted the outcomes and indications. In addition, we aim to summarize real-world evidence that suggests the outcomes among the highly selective phase II studies can be reproduced with commercial CAR T-cell therapy. Despite significant differences in patient characteristics, the adverse events and response rates of patients treated with commercial CAR T-cell therapy are comparable to that of the clinical trials. Without the constraints of a prospective study, we will explore outcomes of special interest populations often excluded from clinical trials treated with commercial CAR T-cell therapy.