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:First-line anti-BCMA CAR-T cell therapy in a fragile patient with biclonal gammopathy and giant plasma cell tumor multiple myeloma with multiple comorbidities: a case report.
First-line anti-BCMA CAR-T cell therapy in a fragile patient with biclonal gammopathy and giant plasma cell tumor multiple myeloma with multiple comorbidities: a case report.
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一线抗 BCMA CAR-T 细胞疗法对高危 MM 患者有效且安全,即使对合并多种基础疾病的虚弱患者也是如此。
靶向B细胞成熟抗原(BCMA)的CAR-T(CAR-T)细胞已用于有效治疗复发/难治性多发性骨髓瘤(MM),但患者复发率仍较高,可能与多线化疗后T细胞质量较差有关。本病例展示了一线抗BCMA CAR-T 治疗高危MM患者(包括伴有衰弱及多种合并症患者)的有效性和安全性。病例介绍:一名75岁女性诊断为双克隆丙种球蛋白病和高危MM,右股骨头有髓外肿块。患者体弱,合并多种疾病,包括肺炎、左下肢深静脉血栓及脑出血继发癫痫。考虑其衰弱及合并症,建议采用商业化全人源抗BCMA CAR-T 产品equecabtagene autoleucel作为一线CAR-T 治疗,患者及家属接受。接受1个周期硼替佐米、环磷酰胺和地塞米松(VCD)后,达到非常好的部分缓解(VGPR);随后进行白细胞单采,收获细胞送至制造商制备。氟达拉滨和环磷酰胺(FC)淋巴细胞清除后,输注equecabtagene autoleucel。输注后第21天达到严格完全缓解(sCR)且微小残留病(MRD)阴性,未发生严重毒性。CAR-T/CD3+ T细胞比例逐渐增加,第14天达峰值54.97%,随后逐渐下降,第153天仍为0.03%。CAR-T 输注7个月后,患者因右髋疼痛接受右髋关节置换及盆腔病灶刮除术,术后病理未见MM细胞。截至目前,无维持治疗下深度缓解已持续12个月。
一线抗BCMA CAR-T 细胞疗法对高危MM患者有效且安全,即使患者体弱并合并多种疾病亦然。
Chimeric antigen receptor T (CAR-T) cells targeting B-cell maturation antigen (BCMA) have been used as an effective therapy against relapsed/refractory multiple myeloma (MM). However, the relapse rates in these patients are still high, which may be related to the poor quality of T cells after multiple chemotherapies. The case reported here demonstrated the effectiveness and safety of first-line anti-BCMA CAR-T cell therapy for high-risk MM patients, even in frailty with multiple comorbidities. CASE PRESENTATION: A 75-year-old woman was diagnosed with biclonal gammopathy and high-risk MM with extramedullary mass in the right caput femoris. The patient was fragile with multiple comorbidities, including pneumonia, left lower limb deep venous thrombosis, and epilepsy secondary to cerebral hemorrhage. Considering the patient's fragility and comorbidities, commercial equecabtagene autoleucel, a fully human anti-BCMA CAR-T cells, as first-line CAR-T cell therapy, was proposed and accepted by the patient and her family. After one cycle of bortezomib, cyclophosphamide, and dexamethasone (VCD) regimen), she reached very good partial response (VGPR). Then her leukapheresis was performed, and the harvested cells were sent to the manufacturer for preparation. After lymphodepletion was performed using fludarabine and cyclophosphamide (FC) chemotherapy, her equecabtagene autoleucel was transfused. On day 21 after infusion, she achieved stringent complete remission (sCR) with minimal residual disease (MRD) negativity without severe toxicity. The CAR-T cells/CD3 + T cell ratio gradually increased, reaching a maximum of 54.97% on day 14, and gradually decreased, remaining at 0.03% on the 153rd day. The patient received right hip replacement plus pelvic lesion curettage 7 months after CAR-T transfusion due to pain in her right hip, but no MM cells were found in postoperative pathology. Hitherto, her deep remission persisted for 12 months without any maintenance therapy.
First-line anti-BCMA CAR-T cell therapy is effective and safe for high-risk MM patients, even in fragile patients with multiple comorbidities.
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