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埃兰妥单抗用于伴有严重肾功能损害且需要血液透析的复发/难治性多发性骨髓瘤

Elranatamab for Relapsed/Refractory Multiple Myeloma With Severe Renal Impairment Requiring Hemodialysis.

作者信息

Hoffmann Michèle, Jeker Barbara, Huynh-Do Uyen, Banz Yara, Godau Jeanne, Weber Elisabeth, Bacher Ulrike, Pabst Thomas

机构信息

Department of Medical Oncology, Inselspital Bern, Bern University Hospital, University of Bern, Bern, Switzerland.

Division of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

出版信息

Hematol Oncol. 2025 Jul;43(4):e70120. doi: 10.1002/hon.70120.

Abstract

Relapsed/refractory multiple myeloma (RRMM) patients with dialysis-dependent renal impairment face limited therapeutic options due to exclusion from clinical trials, a lack of evidence-based guidelines, and inferior outcomes. Bispecific antibodies targeting B-cell maturation antigen (BCMA) have shown promise in RRMM treatment but remain understudied in this vulnerable population. To illustrate this issue, we introduce the case of a 68-year-old female with triple-class RRMM and end-stage renal disease requiring hemodialysis, treated with elranatamab as a second line treatment following progression after therapy with daratumumab, bortezomib, lenalidomide, and dexamethasone. Despite experiencing grade I cytokine release syndrome during the initial administrations, symptoms were managed effectively with tocilizumab and dexamethasone, allowing treatment continuation. The patient achieved a very good partial remission within 7 weeks. Although hemodialysis dependence persisted, the therapy was well-tolerated with manageable adverse events. According to the literature, BCMA-directed immunotherapies, including teclistamab, belantamab mafodotin, and idecabtagene vicleucel, have shown efficacy in dialysis-dependent RRMM patients, though data remain limited. Pharmacokinetic analyses indicate that mild or moderate renal impairment does not have a significant impact on the pharmacokinetics of elranatamab. Although no retrospective studies or case series have investigated the use of elranatamab in dialysis-dependent patients, a single case report suggests that its administration is both feasible and well-tolerated in this population despite the absence of comprehensive pharmacokinetic data. This review highlights feasibility, safety, and encouraging efficacy of elranatamab in managing RRMM in a dialysis-dependent patient, representing the second case report in the literature. By providing real-world evidence for the use of bispecific antibodies in end stage renal disease patients, this review emphasizes the potential for expanding therapeutic options to this vulnerable population while highlighting the need for vigilant monitoring of infection prevention and management. Prospective studies are warranted to validate these findings and optimize therapeutic strategies for patients with RRMM and severe renal impairment.

摘要

因被排除在临床试验之外、缺乏循证指南以及预后较差,依赖透析的肾功能损害的复发/难治性多发性骨髓瘤(RRMM)患者面临的治疗选择有限。靶向B细胞成熟抗原(BCMA)的双特异性抗体在RRMM治疗中已显示出前景,但在这一脆弱人群中的研究仍较少。为说明这一问题,我们介绍一例68岁女性患者,她患有三重耐药RRMM和需要血液透析的终末期肾病,在接受达雷妥尤单抗、硼替佐米、来那度胺和地塞米松治疗进展后,接受elranatamab作为二线治疗。尽管在初始给药期间出现了1级细胞因子释放综合征,但通过托珠单抗和地塞米松有效控制了症状,使治疗得以继续。患者在7周内实现了非常好的部分缓解。尽管仍依赖血液透析,但该治疗耐受性良好,不良事件可控。根据文献,包括替西妥单抗、贝兰他单抗马福多汀和idecabtagene vicleucel在内的靶向BCMA的免疫疗法在依赖透析的RRMM患者中已显示出疗效,不过数据仍然有限。药代动力学分析表明,轻度或中度肾功能损害对elranatamab的药代动力学没有显著影响。尽管尚无回顾性研究或病例系列探讨elranatamab在依赖透析患者中的应用,但一份病例报告表明,尽管缺乏全面的药代动力学数据,但在这一人群中使用elranatamab是可行且耐受性良好的。本综述强调了elranatamab在治疗依赖透析的RRMM患者中的可行性、安全性和令人鼓舞的疗效,这是文献中的第二篇病例报告。通过提供双特异性抗体在终末期肾病患者中应用的真实世界证据,本综述强调了扩大这一脆弱人群治疗选择的潜力,同时突出了对感染预防和管理进行密切监测的必要性。有必要进行前瞻性研究以验证这些发现,并优化RRMM和严重肾功能损害患者的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6cf/12276727/9d84bbdc1ba8/HON-43-e70120-g003.jpg

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