Role of CD19 Chimeric Antigen Receptor T Cells in Second-Line Large B Cell Lymphoma: Lessons from Phase 3 Trials. An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy

Abstract

Since 2017, 3 CD19-directed chimeric antigen receptor (CAR) T cell therapies-axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel-have been approved for relapsed/refractory aggressive diffuse large B cell lymphoma after 2 lines of therapy. Recently, 3 prospective phase 3 randomized clinical trials were conducted to define the optimal second-line treatment by comparing each of the CAR T cell products to the current standard of care: ZUMA-7 for axicabtagene ciloleucel, BELINDA for tisagenlecleucel, and TRANSFORM for lisocabtagene maraleucel. These 3 studies, although largely addressing the same question, had different outcomes, with ZUMA-7 and TRANSFORM demonstrating significant improvement with CD19 CAR T cells in second-line therapy compared with standard of care but BELINDA not showing any benefit. The US Food and Drug Administration has now approved axicabtagene ciloleucel and lisocabtagene maraleucel for LBCL that is refractory to first-line chemoimmunotherapy or relapse occurring within 12 months of first-line chemoimmunotherapy. Following the reporting of these practice changing studies, here a group of experts convened by the American Society for Transplantation and Cellular Therapy provides a comprehensive review of the 3 studies, emphasizing potential differences, and shares perspectives on what these results mean to clinical practice in this new era of treatment of B cell lymphomas.

Keywords: Autologous transplant; CRS; Cellular therapy; Chimeric antigen receptor (CAR) T cells; ICANS; Lymphoma.

Figure 1.

Potential study designs (see text for details).