Cellular Therapy Updates in B-Cell Lymphoma: The State of the CAR-T

SIMPLE SUMMARY: B-cell lymphomas are the most commonly occurring blood cancer and the second leading cause of cancer-related death among blood cancers. Chemotherapy and stem cell transplantation have long served as the standard therapies for relapsed or refractory aggressive B-cell lymphomas with very poor survival, historically. Recently, the development of multiple chimeric antigen receptor T-cell (CAR-T) products has translated into dramatically improved outcomes and survival for patients with relapsed or refractory B-cell lymphoma. Meanwhile, basic, translational and clinical development within the field has progressed rapidly. The aim of this review is to summarize the current state of the art of CAR-T therapies for B-cell lymphomas within this rapidly evolving field, focusing on current United States Food and Drug Administration (US FDA)-approved products and a selection of promising areas of future clinical development. ABSTRACT: Non-Hodgkin Lymphoma accounts for >460,000 cases and >240,000 deaths globally and >77,000 cases and >20,000 deaths in the U.S. annually, with ~85% of cases being B-cell malignancies. Until recently, patients with relapsed/refractory B-cell lymphoma following standard chemotherapy in combination with anti-CD20 monoclonal antibodies and autologous stem cell transplantation experienced a median overall survival (OS) of <6 months. However, with the approval of four different CD-19 CAR-T therapies between 2017 and 2021, approximately 60–80% of patients receiving CAR-T therapy now achieve an objective response with >3 years median OS. Here, we review the current state of the art of CD19 CAR-T therapies for B-cell lymphomas, focusing on current updates in US FDA-approved products, along with their associated efficacy and toxicities. Lastly, we highlight a selection of promising clinical developments in the field, including various novel strategies to increase CAR-T therapy efficacy while mitigating toxicity.