Résumé
Myeloma is a malignancy associated with significant immune dysfunction imparted by both the disease itself as well as many of the immunosuppressive therapies that have been used in the past.The growing body of preclinical data regarding immunoregulatory mechanisms that appear active in myeloma has begun to be translated to clinical trials targeting these signalling axes.This review summarized the current understanding of the basic biology of several immune checkpoint pathways that may be important in myeloma and provide an up-to-date overview of recent and ongoing clinical trials of immune checkpoint inhibitors in myeloma.Finally,several current challenges and possible future direction of immune checkpoint blockade in myeloma will be reviewed.
Résumé
Allogeneic hematopoietic stem cell transplantation and donor lymphocyte infusion for multiple myeloma (MM) can induce graft-versus-myeloma immunity and long-term survival,but limited efficacy and associated toxicities have prevented its widespread application.Cellular immunotherapies and vaccines are explored to induce more specific,reliable,and potent antimyeloma immune responses with less treatmentrelated risk.Advances in molecular biology,basic and applied immunology,have led to several promising approaches such as genetically engineered T cells with chimeric antigen receptors and T-cell receptors targeting myeloma-specific epitopes,vaccine primed ex vivo expanded autologous T cells,expanded marrowinfiltrating lymphocytes,and plasma cell/dendritic cell fusion vaccines.The combination of these emerging therapies to immunomodulatory drugs and inhibitors of programmed death-1 T-cell regulatory pathways could improve the outcome for MM patients.This article reviews the latest progress of cellular and vaccine immunotherapy for MM at the 58th American Society of Hematology (ASH) Annual Meeting,and discusses how these therapies might integrate and synergize with existing treatment paradigms.