CAR T Cells and Other Cellular Therapies for Multiple Myeloma: 2018 Update

Despite advances in therapy, myeloma remains incurable in most patients. Outcomes remain particularly poor for those with adverse cytogenetics or disease that has become resistant to multiple lines of therapy.1 Novel approaches are needed for these populations. Immunologic-based therapies, such as vaccines, immunomodulating antibodies, and cellular therapies, have a unique mechanism of action that may overcome drug resistance and, particularly for cellular therapies, potentially provide long-term tumor surveillance and durable disease control.2 However, widespread clinical application of immune-based approaches for myeloma has been limited either by toxicity (e.g., for allogeneic stem cell transplantation [SCT], PD-1 inhibitors)3,4 or poor/inconsistent efficacy (e.g., for tumor vaccines).5,6 In 2018, that narrative may be changing because of cellular therapies. Cellular therapies fall into two broad categories: (1) non–gene-modified therapies, which rely on the endogenous/native T-cell (or in some cases natural killer cell) repertoire to recognize tumor cells, or (2) gene-modified therapies, in which cells are engineered to express a novel receptor with tumor antigen specificity. The most promising results so far are with gene-modified T cells that express a CAR, and this review will focus primarily on clinical outcomes reported to date with CAR T cells for myeloma, as well as on CAR T cell–related toxicities, outstanding questions, and where the field may be heading next. NON–GENE-MODIFIED T-CELL THERAPIES Section: ChooseTop of pageAbstractNON–GENE-MODIFIED T-CELL ... <