%0 Journal Article
%T CAR T Cells and Other Cellular Therapies for Multiple Myeloma: 2018 Update
%A Adam D. Cohen
%J About the Ed Book | ASCO Educational Book
%D 2018
%R https://doi.org/10.1200/EDBK_200889
%X 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每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每related toxicities, outstanding questions, and where the field may be heading next. NON每GENE-MODIFIED T-CELL THERAPIES Section: ChooseTop of pageAbstractNON每GENE-MODIFIED T-CELL ... <<GENE-MODIFIED T-CELL THER...FUTURE DIRECTIONSCONCLUSIONSReferences Allogeneic SCT was the first cellular therapy for myeloma and remains an option in selected patients; durable long-term remission rates range from 20% to 40% across various studies (all reviewed by Bashir and Qazilbash3). Donor lymphocyte infusion also can induce objective responses, particularly when used for early relapses or residual disease after allogeneic SCT.7,8 Greater adoption of these approaches has been limited by persistent treatment-related mortality rates of 10% to 20% (even with nonmyeloablative conditioning), high rates of chronic graft-versus-host-disease, and inconsistent results in randomized trials compared with autologous SCT approaches.3,9,10 Recent efforts have focused on trying to improve the therapeutic index of this approach via novel graft-versus-host-disease prevention strategies (e.g., T cell每depleted stem cell grafts, post-transplantation cyclophosphamide),11,12 antigen-specific donor
%U http://ascopubs.org/doi/full/10.1200/EDBK_200889