{"title":"抗CD38单克隆抗体对不符合干细胞移植条件的65岁以上复发性或难治性多发性骨髓瘤患者的疗效：倾向评分匹配研究","authors":"Satoshi Yamasaki, Michitoshi Hashiguchi, Nao Yoshida-Sakai, Hiroto Jojima, Koichi Osaki, Takashi Okamura, Yutaka Imamura","doi":"10.3390/hematolrep16040068","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The development of newer agents, including anti-CD38 monoclonal antibodies (mAbs), has significantly improved overall survival (OS) in patients with relapsed or refractory multiple myeloma (RRMM). However, the treatment of older patients with RRMM who are transplant-ineligible remains challenging.</p><p><strong>Methods: </strong>We retrospectively evaluated OS in 78 transplant-ineligible patients with RRMM who were aged ≥ 65 years and treated at our institution between February 2012 and November 2023.</p><p><strong>Results: </strong>Unadjusted OS was significantly longer in the anti-CD38 mAb-exposed group (i.e., those previously treated with daratumumab and receiving isatuximab plus pomalidomide and low-dose dexamethasone because of disease progression during treatment with daratumumab [<i>n</i> = 6], daratumumab plus pomalidomide and low-dose dexamethasone [<i>n</i> = 9], or isatuximab plus pomalidomide and low-dose dexamethasone without daratumumab-exposure [<i>n</i> = 14]) than in the anti-CD38 mAb-naïve group (no exposure to daratumumab or isatuximab [<i>n</i> = 49]) (<i>p</i> < 0.001). To address potential confounder factors associated with use or nonuse of anti-CD38 mAbs, we performed propensity score matching (PSM) using age, sex, performance status, and Geriatric 8 and Instrumental Activities of Daily Living scores. PSM identified 14 subjects from the anti-CD38 mAb-exposed group with baseline characteristics similar to those of 14 subjects from the anti-CD38 mAb-naïve group. After PSM, the adjusted OS was significantly longer in the anti-CD38 mAb-exposed group than in the anti-CD38 mAb-naïve group (<i>p</i> < 0.001).</p><p><strong>Conclusion: </strong>These findings provide insights into the optimal use of anti-CD38 mAbs in patients with RRMM who are transplant-ineligible and aged ≥65 years and on candidates who are appropriate for novel approaches, such as chimeric antigen receptor T-cell or bispecific T-cell engager therapy.</p>","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":"16 4","pages":"714-723"},"PeriodicalIF":1.1000,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587159/pdf/","citationCount":"0","resultStr":"{\"title\":\"Efficacy of Anti-CD38 Monoclonal Antibodies for Relapsed or Refractory Multiple Myeloma in Stem Cell Transplant-Ineligible Patients Aged over 65 Years: A Propensity Score-Matched Study.\",\"authors\":\"Satoshi Yamasaki, Michitoshi Hashiguchi, Nao Yoshida-Sakai, Hiroto Jojima, Koichi Osaki, Takashi Okamura, Yutaka Imamura\",\"doi\":\"10.3390/hematolrep16040068\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The development of newer agents, including anti-CD38 monoclonal antibodies (mAbs), has significantly improved overall survival (OS) in patients with relapsed or refractory multiple myeloma (RRMM). However, the treatment of older patients with RRMM who are transplant-ineligible remains challenging.</p><p><strong>Methods: </strong>We retrospectively evaluated OS in 78 transplant-ineligible patients with RRMM who were aged ≥ 65 years and treated at our institution between February 2012 and November 2023.</p><p><strong>Results: </strong>Unadjusted OS was significantly longer in the anti-CD38 mAb-exposed group (i.e., those previously treated with daratumumab and receiving isatuximab plus pomalidomide and low-dose dexamethasone because of disease progression during treatment with daratumumab [<i>n</i> = 6], daratumumab plus pomalidomide and low-dose dexamethasone [<i>n</i> = 9], or isatuximab plus pomalidomide and low-dose dexamethasone without daratumumab-exposure [<i>n</i> = 14]) than in the anti-CD38 mAb-naïve group (no exposure to daratumumab or isatuximab [<i>n</i> = 49]) (<i>p</i> < 0.001). To address potential confounder factors associated with use or nonuse of anti-CD38 mAbs, we performed propensity score matching (PSM) using age, sex, performance status, and Geriatric 8 and Instrumental Activities of Daily Living scores. PSM identified 14 subjects from the anti-CD38 mAb-exposed group with baseline characteristics similar to those of 14 subjects from the anti-CD38 mAb-naïve group. After PSM, the adjusted OS was significantly longer in the anti-CD38 mAb-exposed group than in the anti-CD38 mAb-naïve group (<i>p</i> < 0.001).</p><p><strong>Conclusion: </strong>These findings provide insights into the optimal use of anti-CD38 mAbs in patients with RRMM who are transplant-ineligible and aged ≥65 years and on candidates who are appropriate for novel approaches, such as chimeric antigen receptor T-cell or bispecific T-cell engager therapy.</p>\",\"PeriodicalId\":12829,\"journal\":{\"name\":\"Hematology Reports\",\"volume\":\"16 4\",\"pages\":\"714-723\"},\"PeriodicalIF\":1.1000,\"publicationDate\":\"2024-11-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587159/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Hematology Reports\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.3390/hematolrep16040068\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hematology Reports","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3390/hematolrep16040068","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景：包括抗CD38单克隆抗体（mAbs）在内的新型药物的开发大大提高了复发性或难治性多发性骨髓瘤（RRMM）患者的总生存率（OS）。然而，对不符合移植条件的老年 RRMM 患者的治疗仍具有挑战性：我们对2012年2月至2023年11月期间在本院接受治疗的78例年龄≥65岁、不符合移植条件的RRMM患者的OS进行了回顾性评估：结果：抗CD38 mAb暴露组（即曾接受达拉曲单抗治疗的患者）的未调整OS明显更长、曾接受过达拉曲单抗治疗的患者在接受达拉曲单抗治疗期间因疾病进展而接受伊沙妥昔单抗联合泊马度胺和小剂量地塞米松治疗[n = 6]、达拉曲单抗联合泊马度胺和小剂量地塞米松治疗[n = 9]或伊沙妥昔单抗联合泊马度胺和小剂量地塞米松治疗[n = 9]、或伊沙妥昔单抗加泊马度胺和小剂量地塞米松，但未接触过达拉atumumab[n = 14]）比抗 CD38 mAb-naïve组（未接触过达拉atumumab或伊沙妥昔单抗[n = 49]）（P < 0.001).为了解决与使用或不使用抗 CD38 mAb 相关的潜在混杂因素，我们使用年龄、性别、表现状态以及老年医学 8 项评分和日常生活工具性活动评分进行了倾向评分匹配（PSM）。PSM从抗CD38 mAb暴露组中确定了14名受试者，其基线特征与抗CD38 mAb未暴露组的14名受试者相似。PSM 后，抗 CD38 mAb 暴露组的调整后 OS 明显长于抗 CD38 mAb 未暴露组（p < 0.001）：这些发现为不符合移植条件且年龄≥65岁的RRMM患者以及适合采用嵌合抗原受体T细胞或双特异性T细胞吞噬疗法等新方法的候选者提供了抗CD38 mAb的最佳使用方法。
Efficacy of Anti-CD38 Monoclonal Antibodies for Relapsed or Refractory Multiple Myeloma in Stem Cell Transplant-Ineligible Patients Aged over 65 Years: A Propensity Score-Matched Study.
Background: The development of newer agents, including anti-CD38 monoclonal antibodies (mAbs), has significantly improved overall survival (OS) in patients with relapsed or refractory multiple myeloma (RRMM). However, the treatment of older patients with RRMM who are transplant-ineligible remains challenging.
Methods: We retrospectively evaluated OS in 78 transplant-ineligible patients with RRMM who were aged ≥ 65 years and treated at our institution between February 2012 and November 2023.
Results: Unadjusted OS was significantly longer in the anti-CD38 mAb-exposed group (i.e., those previously treated with daratumumab and receiving isatuximab plus pomalidomide and low-dose dexamethasone because of disease progression during treatment with daratumumab [n = 6], daratumumab plus pomalidomide and low-dose dexamethasone [n = 9], or isatuximab plus pomalidomide and low-dose dexamethasone without daratumumab-exposure [n = 14]) than in the anti-CD38 mAb-naïve group (no exposure to daratumumab or isatuximab [n = 49]) (p < 0.001). To address potential confounder factors associated with use or nonuse of anti-CD38 mAbs, we performed propensity score matching (PSM) using age, sex, performance status, and Geriatric 8 and Instrumental Activities of Daily Living scores. PSM identified 14 subjects from the anti-CD38 mAb-exposed group with baseline characteristics similar to those of 14 subjects from the anti-CD38 mAb-naïve group. After PSM, the adjusted OS was significantly longer in the anti-CD38 mAb-exposed group than in the anti-CD38 mAb-naïve group (p < 0.001).
Conclusion: These findings provide insights into the optimal use of anti-CD38 mAbs in patients with RRMM who are transplant-ineligible and aged ≥65 years and on candidates who are appropriate for novel approaches, such as chimeric antigen receptor T-cell or bispecific T-cell engager therapy.
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