CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Kidney Transplantation Post-Chimeric Antigen Receptor (CAR) T-Cell Therapy in Multiple Myeloma.
Kidney Transplantation Post-Chimeric Antigen Receptor (CAR) T-Cell Therapy in Multiple Myeloma.
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约半数多发性骨髓瘤(MM)患者患有肾脏疾病,而肾衰竭与预后不良相关。由于担心疾病复发、感染和移植物排斥,MM患者很少接受肾移植。
然而,包括靶向B细胞成熟抗原(BCMA)的嵌合抗原受体(CAR)T细胞疗法在内的治疗进展,已带来深度且持久的血液学应答,使部分患者获得新的移植机会。
我们报告一例71岁男性患者,患III期MM并具有高危细胞遗传学特征[del(17p)],治疗期间进展为终末期肾病并需血液透析。尽管接受多线治疗,此前从未达到深度缓解;接受西达基奥仑赛(cilta-cel)CAR-T 细胞治疗后,达到微小残留病(MRD)阴性状态。CAR-T 治疗一年后,患者接受活体供肾移植,诱导免疫抑制采用巴利昔单抗,维持治疗采用他克莫司/吗替麦考酚酯。病程中出现低丙种球蛋白血症、血细胞减少、BK病毒血症和急性排斥反应,均通过调整免疫抑制和支持治疗得到管理。移植后17个月,移植物功能仍稳定(肌酐1.8 mg/dL),且患者达到MRD阴性完全血液学缓解。本病例揭示了MM患者CAR-T 治疗后进行肾移植的可行性及面临的挑战。
Kidney disease affects approximately half of patients with multiple myeloma (MM), and kidney failure is associated with poor prognosis. Kidney transplantation is rarely pursued in MM owing to concerns of relapse, infection, and allograft rejection.
However, advances in therapy, including B-cell maturation antigen-directed chimeric antigen receptor (CAR) T-cell therapy, have led to deep and durable hematologic responses, creating new opportunities for transplantation in select patients.
We report a 71-year-old man with stage III MM and high-risk cytogenetics [del(17p)] who developed end-stage kidney disease requiring hemodialysis during his treatment course. Despite multiple lines of therapy, he had never achieved a deep remission until he received ciltacabtagene autoleucel (cilta-cel) CAR T-cell therapy, which led to minimal residual disease (MRD)-negative disease status. One year following CAR T-cell therapy, he underwent living donor kidney transplantation with basiliximab induction, and tacrolimus/mycophenolate maintenance immunosuppression.
His course was complicated by hypogammaglobulinemia, cytopenia, BK viremia, and acute rejection, all managed with immunosuppression adjustment and supportive therapies. At 17 months post-transplant, allograft function remains stable (creatinine 1. 8 mg/dL), and he has achieved an MRD-negative, complete hematologic remission. This case highlights both the feasibility and the challenges of kidney transplantation after CAR T-cell therapy in MM.
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