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.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Myelodysplastic Syndrome Secondary to Chimeric Antigen Receptor T-cell (CAR-T) Therapy for the Treatment of Relapsed/Refractory Multiple Myeloma.
Myelodysplastic Syndrome Secondary to Chimeric Antigen Receptor T-cell (CAR-T) Therapy for the Treatment of Relapsed/Refractory Multiple Myeloma.
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我们报告一例65岁男性复发/难治性多发性骨髓瘤(RRMM)患者,在接受idecabtagene vicleucel(ide-cel)CAR-T 细胞治疗后发生治疗相关骨髓增生异常综合征(MDS)。该患者于2019年初次诊断,接受过多线治疗,包括高剂量美法仑联合自体干细胞移植,随后因疾病进展接受ide-cel治疗。尽管初期获得缓解,第100天骨髓活检显示MDS伴7q缺失,该细胞遗传学异常在此前骨髓评估中未曾出现。虽然CAR-T 疗法已革新了RRMM的治疗,但治疗相关血液系统恶性肿瘤等长期并发症仍未被充分认识。CAR-T 输注与新出现的治疗诱导性细胞遗传学异常之间的时间关系,令人担忧可能是CAR-T 应激暴露了既存的髓系克隆,或是在一例经重度预处理的患者中加速了治疗诱导性髓系肿瘤的发生。本病例说明有必要为CAR-T 接受者制定标准化的恶性肿瘤筛查和长期监测指南。
进一步研究对于明确CAR-T 接受者继发性恶性肿瘤的发生时间、机制和危险因素至关重要。
We present the case of a 65-year-old man with relapsed/refractory multiple myeloma (RRMM) who developed therapy-related myelodysplastic syndrome (MDS) following chimeric antigen receptor T-cell (CAR-T) therapy with idecabtagene vicleucel (ide-cel). The patient, initially diagnosed in 2019, underwent multiple lines of therapy, including high-dose melphalan with autologous stem cell transplantation, before receiving ide-cel for progressive disease. Despite initial remission, a day 100 bone marrow biopsy revealed MDS with a 7q deletion, a cytogenetic abnormality not present on prior marrow evaluations.
While CAR-T therapy has revolutionized RRMM treatment, long-term complications such as therapy-related hematologic malignancy remain under-recognized.
The temporal relationship between CAR-T infusion and the emergence of a new therapy-induced cytogenetic abnormality raises concern for either CAR-T stress revealing a pre-existing myeloid clone or acceleration of therapy-induced myeloid neoplasia in a heavily pretreated patient. This case illustrates the need for standardized guidelines for malignancy screenings and long-term monitoring in CAR-T recipients.
Further studies are essential to delineate the timing, mechanisms, and risk factors for secondary malignancies in CAR-T recipients.
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