Graft-versus-host disease after chimeric antigen receptor T-cell therapy

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the management of relapsed/refractory hematologic malignancies, paving the way for new treatment protocols and therapeutic strategies. Traditionally, only autologous CAR T-cell therapy has been integrated into clinical practice; however, the hefty production costs and considerable delay to treatment significantly limit its accessibility to patients. The incipience of allogeneic CAR T cells is a nascent development in immunotherapy, with the ability to generate universal “off-the-shelf” CAR T cells potentially bridging these long-standing limitations of autologous CAR T-cell therapy. With growing interest in this novel therapy, it has become crucial to fully understand its safety and toxicity profiles, particularly the potential for graft-versus-host disease (GVHD) in recipients with and without previous allogeneic hematopoietic stem cell transplants. In this review, we discuss the risk of GVHD in (1) patients receiving universal CAR T-cell therapy, (2) patients receiving donor-derived CAR T-cell therapy, and (3) patients receiving recipient-derived CAR T-cell therapy.