{"title":"多发性骨髓瘤的细胞疗法:现在是什么,下一步是什么。","authors":"Paula Rodriguez-Otero, Jesús F San-Miguel","doi":"10.1182/hematology.2022000396","DOIUrl":null,"url":null,"abstract":"<p><p>Despite significant improvement in the treatment of multiple myeloma (MM), a cure remains elusive, and patients failing proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies remain a challenge due to a lack of standard of care treatment and a dismal survival rate. The development of T-cell redirecting therapies, including bispecific T-cell engagers and chimeric antigen receptor (CAR) T cells, have transformed the outcome of triple-class exposed relapsed and refractory MM (RRMM). B-cell maturation antigen (BCMA) has proven to be an important target in MM, and BCMA-directed CAR T cells have shown unprecedented efficacy with a prolonged duration of response in a population with advanced RRMM, leading to the approval of 2 different BCMA CAR T-cell products. Still, and in contrast to prior experience in the field of CD19-directed CARs, no plateau has been seen in the survival curves, and relapses continue to occur. Therefore, further improvement is needed. Early use in the course of the disease as well as of next- generation CARs may further augment the efficacy of these therapies. In this review we address current state-of-the-art approved BCMA-directed CAR T-cell therapy in RRMM, as well as potential future developments focused on optimizing patient care and novel CAR designs.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":null,"pages":null},"PeriodicalIF":2.9000,"publicationDate":"2022-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820257/pdf/hem.2022000396.pdf","citationCount":"7","resultStr":"{\"title\":\"Cellular therapy for multiple myeloma: what's now and what's next.\",\"authors\":\"Paula Rodriguez-Otero, Jesús F San-Miguel\",\"doi\":\"10.1182/hematology.2022000396\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Despite significant improvement in the treatment of multiple myeloma (MM), a cure remains elusive, and patients failing proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies remain a challenge due to a lack of standard of care treatment and a dismal survival rate. The development of T-cell redirecting therapies, including bispecific T-cell engagers and chimeric antigen receptor (CAR) T cells, have transformed the outcome of triple-class exposed relapsed and refractory MM (RRMM). B-cell maturation antigen (BCMA) has proven to be an important target in MM, and BCMA-directed CAR T cells have shown unprecedented efficacy with a prolonged duration of response in a population with advanced RRMM, leading to the approval of 2 different BCMA CAR T-cell products. Still, and in contrast to prior experience in the field of CD19-directed CARs, no plateau has been seen in the survival curves, and relapses continue to occur. Therefore, further improvement is needed. Early use in the course of the disease as well as of next- generation CARs may further augment the efficacy of these therapies. In this review we address current state-of-the-art approved BCMA-directed CAR T-cell therapy in RRMM, as well as potential future developments focused on optimizing patient care and novel CAR designs.</p>\",\"PeriodicalId\":12973,\"journal\":{\"name\":\"Hematology. American Society of Hematology. Education Program\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2022-12-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820257/pdf/hem.2022000396.pdf\",\"citationCount\":\"7\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Hematology. American Society of Hematology. Education Program\",\"FirstCategoryId\":\"95\",\"ListUrlMain\":\"https://doi.org/10.1182/hematology.2022000396\",\"RegionNum\":3,\"RegionCategory\":\"教育学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"EDUCATION, SCIENTIFIC DISCIPLINES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hematology. American Society of Hematology. Education Program","FirstCategoryId":"95","ListUrlMain":"https://doi.org/10.1182/hematology.2022000396","RegionNum":3,"RegionCategory":"教育学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"EDUCATION, SCIENTIFIC DISCIPLINES","Score":null,"Total":0}
引用次数: 7
摘要
尽管多发性骨髓瘤(MM)的治疗有了显著的改善,但治愈仍然是难以捉摸的,由于缺乏标准的护理治疗和低生存率,患者失败的蛋白酶体抑制剂,免疫调节药物和抗cd38单克隆抗体仍然是一个挑战。T细胞重定向疗法的发展,包括双特异性T细胞接合物和嵌合抗原受体(CAR) T细胞,已经改变了三级暴露的复发和难治性MM (RRMM)的结局。b细胞成熟抗原(BCMA)已被证明是MM的重要靶点,而BCMA导向的CAR - T细胞在晚期RRMM患者中显示出前所未有的疗效,反应时间延长,导致两种不同的BCMA CAR - T细胞产品获批。尽管如此,与cd19靶向car领域的先前经验相反,在生存曲线中没有看到平台,并且复发继续发生。因此,需要进一步改进。在疾病过程中早期使用以及下一代car可能会进一步增强这些疗法的疗效。在这篇综述中,我们讨论了目前最先进的bcma靶向CAR -t细胞治疗RRMM,以及潜在的未来发展,重点是优化患者护理和新型CAR设计。
Cellular therapy for multiple myeloma: what's now and what's next.
Despite significant improvement in the treatment of multiple myeloma (MM), a cure remains elusive, and patients failing proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies remain a challenge due to a lack of standard of care treatment and a dismal survival rate. The development of T-cell redirecting therapies, including bispecific T-cell engagers and chimeric antigen receptor (CAR) T cells, have transformed the outcome of triple-class exposed relapsed and refractory MM (RRMM). B-cell maturation antigen (BCMA) has proven to be an important target in MM, and BCMA-directed CAR T cells have shown unprecedented efficacy with a prolonged duration of response in a population with advanced RRMM, leading to the approval of 2 different BCMA CAR T-cell products. Still, and in contrast to prior experience in the field of CD19-directed CARs, no plateau has been seen in the survival curves, and relapses continue to occur. Therefore, further improvement is needed. Early use in the course of the disease as well as of next- generation CARs may further augment the efficacy of these therapies. In this review we address current state-of-the-art approved BCMA-directed CAR T-cell therapy in RRMM, as well as potential future developments focused on optimizing patient care and novel CAR designs.