Multiple myeloma(MM),considered an incurable hematological malignancy,is characterized by its clonal evolution of malignant plasma cells.Although the application of autologous stem cell transplantation(ASCT)and the in...Multiple myeloma(MM),considered an incurable hematological malignancy,is characterized by its clonal evolution of malignant plasma cells.Although the application of autologous stem cell transplantation(ASCT)and the introduction of novel agents such as immunomodulatory drugs(IMiDs)and proteasome inhibitors(PIs)have doubled the median overall survival to eight years,relapsed and refractory diseases are still frequent events in the course of MM.To achieve a durable and deep remission,immunotherapy modalities have been developed for relapsed/refractory multiple myeloma(RRMM).Among these approaches,chimeric antigen receptor(CAR)T-cell therapy is the most promising star,based on the results of previous success in B-cell neoplasms.In this immunotherapy,autologous T cells are engineered to express an artificial receptor which targets a tumor-associated antigen and initiates the T-cell killing procedure.Tisagenlecleucel and Axicabtagene,targeting the CD19 antigen,are the two pacesetters of CAR T-cell products.They were approved by the US Food and Drug Administration(FDA)in 2017 for the treatment of acute lymphocytic leukemia(ALL)and diffuse large B-cell lymphoma(DLBCL).Their development enabled unparalleled efficacy in combating hematopoietic neoplasms.In this review article,we summarize six promising candidate antigens in MM that can be targeted by CARs and discuss some noteworthy studies of the safety profile of current CAR T-cell therapy.展开更多
Treatment of multiple myeloma(MM)has advanced dramatically in the past two decades.However,under the conditions of the COVID-19 pandemic,treatment strategies have been modified accordingly.Numerous novel agents,update...Treatment of multiple myeloma(MM)has advanced dramatically in the past two decades.However,under the conditions of the COVID-19 pandemic,treatment strategies have been modified accordingly.Numerous novel agents,updated trials,and major advances in myeloma have been reported in the American Society of Hematology 2020 annual meeting,either for transplant-eligible or ineligible patients.Hot topics such as the significance of autologous stem cell transplantation(ASCT),development of novel agents,and chimeric antigen receptor-T(CAR-T)cells have been widely discussed.The triplet regimen bortezomib,lenalidomide,and dexamethasone(VRd)is recommended as the standard first-line treatment,and the addition of a fourth drug improves efficacy and survival.The value of ASCT remains undoubtful,even in the era of quadruplet induction.Dual-drug maintenance,including proteasome inhibitors and immunomodulatory drugs,overcomes unfavorable outcomes in high-risk patients.For relapsed/refractory myeloma(RRMM)patients,novel agents such as selinexor and venetoclax are superior.CAR-T cells and other cell-surface-targeted therapies also appear promising.展开更多
文摘Multiple myeloma(MM),considered an incurable hematological malignancy,is characterized by its clonal evolution of malignant plasma cells.Although the application of autologous stem cell transplantation(ASCT)and the introduction of novel agents such as immunomodulatory drugs(IMiDs)and proteasome inhibitors(PIs)have doubled the median overall survival to eight years,relapsed and refractory diseases are still frequent events in the course of MM.To achieve a durable and deep remission,immunotherapy modalities have been developed for relapsed/refractory multiple myeloma(RRMM).Among these approaches,chimeric antigen receptor(CAR)T-cell therapy is the most promising star,based on the results of previous success in B-cell neoplasms.In this immunotherapy,autologous T cells are engineered to express an artificial receptor which targets a tumor-associated antigen and initiates the T-cell killing procedure.Tisagenlecleucel and Axicabtagene,targeting the CD19 antigen,are the two pacesetters of CAR T-cell products.They were approved by the US Food and Drug Administration(FDA)in 2017 for the treatment of acute lymphocytic leukemia(ALL)and diffuse large B-cell lymphoma(DLBCL).Their development enabled unparalleled efficacy in combating hematopoietic neoplasms.In this review article,we summarize six promising candidate antigens in MM that can be targeted by CARs and discuss some noteworthy studies of the safety profile of current CAR T-cell therapy.
文摘Treatment of multiple myeloma(MM)has advanced dramatically in the past two decades.However,under the conditions of the COVID-19 pandemic,treatment strategies have been modified accordingly.Numerous novel agents,updated trials,and major advances in myeloma have been reported in the American Society of Hematology 2020 annual meeting,either for transplant-eligible or ineligible patients.Hot topics such as the significance of autologous stem cell transplantation(ASCT),development of novel agents,and chimeric antigen receptor-T(CAR-T)cells have been widely discussed.The triplet regimen bortezomib,lenalidomide,and dexamethasone(VRd)is recommended as the standard first-line treatment,and the addition of a fourth drug improves efficacy and survival.The value of ASCT remains undoubtful,even in the era of quadruplet induction.Dual-drug maintenance,including proteasome inhibitors and immunomodulatory drugs,overcomes unfavorable outcomes in high-risk patients.For relapsed/refractory myeloma(RRMM)patients,novel agents such as selinexor and venetoclax are superior.CAR-T cells and other cell-surface-targeted therapies also appear promising.
