Abstract IA12: CAR T-cell therapy for lymphoma and multiple myeloma

Abstract

Chimeric antigen receptors (CARs) are fusion proteins that incorporate antigen-binding domains and T-cell signaling domains. The first CAR T cells to be shown to be clinically effective targeted the B-cell antigen CD19. Anti-CD19 CAR T cells have been effective against all major types of B-cell lymphomas, and anti-CD19 CAR T cells have now obtained Food and Drug Administration (FDA) approval for treatment of the most common type of lymphoma, diffuse large B-cell lymphoma. This approval was based on clinical results that showed an approximately 50% complete remission rate of anti-CD19 CAR T-cell therapy for diffuse large B-cell lymphoma. These responses have been durable. Eleven of twelve patients who obtained complete remissions on a phase 1 trial of anti-CD19 CAR T cells are still progression-free 13 to 36 months after treatment (Kochenderfer et al. Journal of Clinical Oncology, 2017). Even more durable remissions have occurred in a small number of patients in an early cohort of anti-CD19 CAR therapy. Four patients with remissions of 38 to 56 months will be presented. These patients are particularly interesting because 3 of the 4 patients with long remissions have had recovery of normal B cells while the complete remissions have continued. This result shows that remissions of diffuse large B-cell lymphoma can continue after disappearance of a functional anti-CD19 CAR T-cell response. Beyond CD19, active CAR T-cell therapy for multiple myeloma has been developed by targeting B-cell maturation antigen (BCMA). Anti-BCMA CAR T cells have undergone rapid clinical development since first being reported in 2013 (Carpenter et al. Clinical Cancer Research, 2013). Clinical results of the first-in-humans clinical trial of anti-BCMA CARs (Brudno et al. Journal of Clinical Oncology, 2018) will be presented, and future plans for multiple myeloma CAR T-cell therapies will be discussed. Citation Format: James N. Kochenderfer. CAR T-cell therapy for lymphoma and multiple myeloma [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr IA12.