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:How we manage multiple myeloma with clonal hematopoiesis of indeterminate potential (CHIP): a case report.
How we manage multiple myeloma with clonal hematopoiesis of indeterminate potential (CHIP): a case report.
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本病例报告强调了合并 CHIP 时 MM 管理的复杂性,提示 HSCT 和 CAR-T 细胞疗法的潜在效用。
意义未明的克隆性造血(CHIP)以血液系统肿瘤相关基因改变为特征,在同时患有血液系统恶性肿瘤时会带来临床管理挑战。CHIP可能影响疾病进展和治疗应答,使治疗决策更为复杂。我们报告一例携带CHIP相关PPM1D突变的73岁多发性骨髓瘤(MM)男性患者,阐述此类病例的复杂性及治疗考量。 病例描述:接受4个周期的环磷酰胺、硼替佐米和地塞米松治疗后,患者达到部分缓解;随后接受8个周期来那度胺、地塞米松和硼替佐米治疗,获得血液学完全缓解(CR)。尽管如此,由于检测到PPM1D相关CHIP,起初认为不适合直接进行自体造血干细胞移植(HSCT)。患者在克隆演化并出现侵袭性复发后接受HSCT,但应答持续时间较短。经过超过4线治疗后,患者接受CAR-T(CAR-T)细胞疗法(西达基奥仑赛)作为挽救治疗。该疗法成功诱导缓解,且缓解维持了6个月。
本病例报告凸显合并CHIP的MM管理复杂性,并提示HSCT和CAR-T 细胞疗法可能具有应用价值。仍需前瞻性研究评估这些疗法用于合并CHIP的骨髓瘤患者时的安全性和疗效,以优化治疗策略并改善这一临床难题中的患者结局。
Clonal hematopoiesis of indeterminate potential (CHIP) is characterized by genetic alterations associated with hematologic neoplasms, posing clinical challenges in managing concurrent hematological malignancies. CHIP may complicate the treatment landscape due to its potential to influence disease progression and treatment response. We report a 73-year-old male with multiple myeloma (MM) harboring a CHIP PPM1D mutation, elucidating the complexities and therapeutic considerations in such cases. CASE DESCRIPTION: After four cycles of cyclophosphamide, bortezomib, and dexamethasone therapy, he achieved a partial response, followed by complete hematologic response (CR) post eight cycles of lenalidomide, dexamethasone, and bortezomib therapy. Despite this, upfront autologous hematopoietic stem cell transplantation (HSCT) was initially deemed unsuitable due to positive PPM1D CHIP status. HSCT proceeded after aggressive relapse with clonal evolution but yielded short-lived response. Following failure of >4 lines of therapy, he received chimeric antigen receptor T (CAR-T) cell therapy (ciltacabtagene autoleucel) for salvage. This approach successfully induced remission, which was maintained for 6 months.
This case report highlights MM management complexities in CHIP presence, suggesting potential utility of HSCT and CAR-T cell therapy. Prospective studies are necessary to evaluate the safety and efficacy of these therapies in myeloma patients with concurrent CHIP, aiming to optimize treatment strategies and improve outcomes in this challenging clinical context.
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