Chimeric Antigen Receptor T Cells for B-Cell Lymphoma

Anti-CD19-directed chimeric antigen receptor (CAR) T-cell therapy yields durable remissions in up to 40% of patients with chemoresistant aggressive B-cell non-Hodgkin lymphoma (NHL), a group of patients expected only to survive on average 6 months. Although longer follow-up is needed to define durability, CD19 CAR T cells are demonstrating similar promise in other B-NHL subtypes such as mantle cell lymphoma and the indolent B-cell NHLs. This transformative therapy, however, remains hamstrung by its associated toxicities of cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, as well as by mechanisms of resistance and relapse and accessibility. To address these limitations, studies are underway to investigate toxicity prevention and mitigation strategies and the development of safer CARs, combination strategies to overcome T-cell exhaustion and dual antigen targeting to combat antigen loss, and alternative cell sources to address cost and manufacturing inefficiencies and resolve issues surrounding T-cell fitness.