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嵌合抗原受体(CAR)T细胞疗法在接受维持性血液透析的多发性骨髓瘤和肾衰竭患者中的应用:2例报告

Chimeric Antigen Receptor (CAR) T-Cell Therapy Use in Patients with Multiple Myeloma and Kidney Failure on Maintenance Hemodialysis: A Report of 2 Cases.

作者信息

Pak Wai Lun Will, Brumwell Natalie A, Kabel Charlene C, Gutgarts Victoria, Jaffer Sathick Insara, Mailankody Sham, Lesokhin Alexander M, Landau Heather J, Shaikh Aisha

机构信息

Renal Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.

Department of Pharmacy, Memorial Sloan Kettering Cancer Center, New York, NY.

出版信息

Kidney Med. 2024 Jun 14;6(8):100856. doi: 10.1016/j.xkme.2024.100856. eCollection 2024 Aug.

DOI:10.1016/j.xkme.2024.100856
PMID:39100867
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11295848/
Abstract

Chimeric antigen receptor (CAR) T-cell therapy against B-cell maturation antigen is a new treatment modality for relapsed or refractory multiple myeloma (MM). Patients with kidney failure and MM were excluded from the pivotal CAR T-cell therapy clinical trials: KaRMMa (idecabtagene vicleucel) and CARTITUDE (ciltacabtagene autocleucel). The safety and efficacy of CAR T-cell therapy in patients with relapsed or refractory MM and kidney failure are limited to a few case reports using idecabtagene vicleucel. Here, we report the first 2 cases of ciltacabtagene autoleucel use in patients with kidney failure on maintenance hemodialysis and relapsed or refractory MM. Both patients achieved a hematologic response following ciltacabtagene autoleucel administration without serious adverse events. These findings suggest that ciltacabtagene autoleucel may be safe and effective in patients with relapsed or refractory MM and kidney failure. In this report, we review the available literature regarding the use of CAR T-cell therapy in patients with MM and kidney failure. We also discuss the modification of the lymphodepletion regimen in the kidney failure setting.

摘要

针对B细胞成熟抗原的嵌合抗原受体(CAR)T细胞疗法是复发或难治性多发性骨髓瘤(MM)的一种新治疗方式。肾衰竭合并MM的患者被排除在关键的CAR T细胞疗法临床试验之外:KaRMMa(idecabtagene vicleucel)和CARTITUDE(cilta-cabtagene autocleucel)。CAR T细胞疗法在复发或难治性MM合并肾衰竭患者中的安全性和有效性仅限于少数使用idecabtagene vicleucel的病例报告。在此,我们报告了首例2例接受维持性血液透析且患有复发或难治性MM的肾衰竭患者使用cilta-cabtagene autoleucel的病例。两名患者在接受cilta-cabtagene autoleucel治疗后均获得血液学缓解,且未出现严重不良事件。这些发现表明,cilta-cabtagene autoleucel在复发或难治性MM合并肾衰竭患者中可能是安全有效的。在本报告中,我们回顾了关于MM合并肾衰竭患者使用CAR T细胞疗法的现有文献。我们还讨论了在肾衰竭情况下淋巴细胞清除方案的调整。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eabd/11295848/7c5974f77204/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eabd/11295848/cb784cc86d9a/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eabd/11295848/7c5974f77204/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eabd/11295848/cb784cc86d9a/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eabd/11295848/7c5974f77204/gr2.jpg

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本文引用的文献

1
Idecabtagene vicleucel chimeric antigen receptor T-cell therapy for relapsed/refractory multiple myeloma with renal impairment.伊达基奥仑赛嵌合抗原受体 T 细胞疗法治疗伴有肾功能损害的复发/难治性多发性骨髓瘤。
Haematologica. 2024 Mar 1;109(3):777-786. doi: 10.3324/haematol.2023.283940.
2
Management of multiple myeloma-related renal impairment: recommendations from the International Myeloma Working Group.多发性骨髓瘤相关肾损害的管理:国际骨髓瘤工作组的建议。
Lancet Oncol. 2023 Jul;24(7):e293-e311. doi: 10.1016/S1470-2045(23)00223-1.
3
Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma.
西达基奥仑赛或标准护理用于来那度胺难治性多发性骨髓瘤。
N Engl J Med. 2023 Jul 27;389(4):335-347. doi: 10.1056/NEJMoa2303379. Epub 2023 Jun 5.
4
Dose recommendations for anticancer drugs in patients with renal or hepatic impairment: an update.肾或肝功能损害患者抗癌药物的剂量推荐:最新进展
Lancet Oncol. 2023 Jun;24(6):e229. doi: 10.1016/S1470-2045(23)00216-4.
5
Safe and successful CAR T-cell therapy targeting BCMA in a multiple myeloma patient requiring hemodialysis.在一名需要血液透析的多发性骨髓瘤患者中,针对B细胞成熟抗原(BCMA)进行安全且成功的嵌合抗原受体T细胞(CAR T)疗法。
Ann Hematol. 2023 May;102(5):1269-1270. doi: 10.1007/s00277-023-05163-z. Epub 2023 Mar 17.
6
Ide-cel or Standard Regimens in Relapsed and Refractory Multiple Myeloma.伊达赛利珠单抗或标准方案治疗复发/难治性多发性骨髓瘤。
N Engl J Med. 2023 Mar 16;388(11):1002-1014. doi: 10.1056/NEJMoa2213614. Epub 2023 Feb 10.
7
Outcomes of CD19-Targeted Chimeric Antigen Receptor T Cell Therapy for Patients with Reduced Renal Function Including Dialysis.针对包括透析患者在内的肾功能降低患者的 CD19 靶向嵌合抗原受体 T 细胞治疗的结果。
Transplant Cell Ther. 2022 Dec;28(12):829.e1-829.e8. doi: 10.1016/j.jtct.2022.09.009. Epub 2022 Sep 26.
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Four-year follow-up of LCAR-B38M in relapsed or refractory multiple myeloma: a phase 1, single-arm, open-label, multicenter study in China (LEGEND-2).在中国开展的一项 1 期、单臂、开放标签、多中心研究(LEGEND-2)中,评估 LCAR-B38M 治疗复发/难治性多发性骨髓瘤的 4 年随访结果。
J Hematol Oncol. 2022 Jul 6;15(1):86. doi: 10.1186/s13045-022-01301-8.
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Successful administration of chimeric antigen receptor (CAR) T-cell therapy in patients requiring hemodialysis.在需要血液透析的患者中成功实施嵌合抗原受体(CAR)T细胞疗法。
Exp Hematol Oncol. 2022 Feb 28;11(1):10. doi: 10.1186/s40164-022-00266-1.
10
Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study.西达基奥仑赛,一种针对 B 细胞成熟抗原的嵌合抗原受体 T 细胞疗法,用于治疗复发或难治性多发性骨髓瘤患者(CARTITUDE-1):一项 1b/2 期开放标签研究。
Lancet. 2021 Jul 24;398(10297):314-324. doi: 10.1016/S0140-6736(21)00933-8. Epub 2021 Jun 24.