Chimeric Antigen Receptor T Cell Therapy versus Hematopoietic Stem Cell Transplantation: An Evolving Perspective

Cellular therapy modalities, including autologous (auto-) hematopoietic cell transplantation (HCT), allogeneic (allo-) HCT, and now chimeric antigen receptor (CAR) T cell therapy, have demonstrated long-term remission in advanced hematologic malignancies. Auto-HCT and allo-HCT, through hematopoietic rescue, have permitted the use of higher doses of chemotherapy. Allo-HCT also introduced a nonspecific immune-mediated targeting of malignancy resulting in protection from relapse, although at the expense of similar targeting of normal host cells. In contrast, CAR T therapy, through genetically engineered immunotherapeutic precision, allows for redirection of autologous immune effector cells against malignancy in an antigen-specific and MHC-independent fashion, with demonstrated efficacy in patients who are refractory to cytotoxic chemotherapy. It too has unique toxicities and challenges, however. Non-Hodgkin lymphoma (including large B cell lymphoma, mantle cell lymphoma, and follicular lymphoma), B cell acute lymphoblastic leukemia, and multiple myeloma are the 3 main diseases associated with the use of fully developed CAR T products with widespread deployment. Recent and ongoing clinical trials have been examining the interface among the 3 cellular therapy modalities (auto-HCT, allo-HCT, and CAR T) to determine whether they should be “complementary” or “competitive” therapies. In this review, we examine the current state of this interface with respect to the most recent data and delve into the controversies and conclusions that may inform clinical decision making.