CAR T cells as a second-line therapy for large B-cell lymphoma: a paradigm shift?

The standard of care treatment strategy for patients with relapsed or refractory large B-cell lymphoma (LBCL) has been high dose chemotherapy followed by autologous stem cell transplantation (ASCT) if chemotherapy-sensitive in suitable patients. Due to treatment intensity, this approach has only been feasible in half of patients, and due to chemotherapy-resistance has only been successful in a quarter of transplant-eligible patients. Chimeric antigen receptor (CAR) T-cell therapy, using genetically modified autologous T-cells targeting CD19 has been approved for third-line therapy of LBCL, and has been associated with durable remissions in a proportion of patients. In this review, we interpret the design and results of three randomized phase 3 trials comparing CAR T-cell therapy and ASCT, and their implications for CAR T-cell therapy as a potential new standard of care for second-line treatment in appropriate patients with refractory or early relapsing LBCL.