CAR-T Cellular Therapies for Multiple Myeloma

Allogeneic hematopoietic cell transplantation for myeloma can lead to graft-vs-myeloma immunity and long-term survivorship, but limited efficacy and associated toxicities have prevented its widespread use. Cellular immunotherapies seek to induce more specific, reliable and potent anti-myeloma immune responses with less treatment-related risk than is possible with allogeneic transplantation. Transduction of autologous T cells to express antigen-specific chimeric antigen receptors (CARs) is a promising immunotherapeutic approach for B-cell malignancies including multiple myeloma and early clinical results are promising. Other strategies under development include infusion of vaccine-primed and ex vivo expanded/costimulated autologous T cells, genetic engineering of autologous T cells with receptors for myeloma-specific epitopes (TCRs), administration of DC/plasma cell fusions and administration expanded marrow-infiltrating lymphocytes. These in addition to novel immunomodulatory drugs such as inhibitors of the programmed death-1 T cell regulatory pathway may synergize and enhance CAR-T cellular immunotherapies.