决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Relapsed/refractory multiple myeloma with extramedullary plasmacytomas successfully rechallenged with humanized B-cell maturation antigen-directed chimeric antigen receptor T-cell immunotherapy in an advanced disease stage: A case report.
这些发现支持进一步研究再治疗策略和CAR-T后维持治疗方法。
多发性骨髓瘤(MM)是一种浆细胞恶性肿瘤,而髓外浆细胞瘤(EMP)与侵袭性生物学行为和不良预后相关。靶向B细胞成熟抗原(BCMA)的CAR-T 细胞疗法在复发/难治性MM(RRMM)中已显示出显著活性;然而,在EMP患者中,尤其是在既往接受过BCMA CAR-T治疗后的患者中,证据仍然有限。本研究描述了一例38岁男性RRMM伴广泛颅部EMP患者,其在接受多种既往治疗后出现疾病进展,包括基于蛋白酶体抑制剂和免疫调节药物的方案、抗CD38治疗、基于卡非佐米的治疗以及既往非人源化BCMA CAR-T产品。由于疾病快速进展,该患者接受了桥接减瘤治疗,随后接受全人源化BCMA CAR-T疗法(equecabtagene autoleucel)。输注后,血清和尿液M蛋白水平迅速下降,颅面部肿块在临床和影像学上均消退。患者在随访期间达到严格完全缓解,髓外病变获得持久控制。本病例提示,全人源化BCMA CAR-T疗法在部分RRMM伴EMP患者中可能仍然有效,即使在既往非人源化BCMA CAR-T治疗失败后也是如此。这些发现支持进一步研究再治疗策略和CAR-T后维持治疗方法。
Multiple myeloma (MM) is a plasma cell malignancy, and extramedullary plasmacytoma (EMP) is associated with an aggressive biology and poor outcomes. B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell (CAR-T) therapy has shown substantial activity in relapsed/refractory MM (RRMM); however, evidence in patients with EMP, particularly after prior BCMA CAR-T exposure, remains limited. The present study describes the case of a 38-year-old man with RRMM and extensive cranial EMP who progressed after multiple prior therapies, including proteasome inhibitor- and immunomodulatory drug-based regimens, anti-CD38 therapy, carfilzomib-based therapy and a previous non-humanized BCMA CAR-T product. Due to rapidly progressive disease, the patient received bridging cytoreduction followed by fully humanized BCMA CAR-T therapy (equecabtagene autoleucel). After infusion, serum and urine M-protein levels rapidly declined and the craniofacial mass regressed clinically and radiographically. The patient achieved stringent complete response with durable control of extramedullary disease during follow-up. The present case suggests that fully humanized BCMA CAR-T therapy may remain effective in selected patients with RRMM and EMP, even after prior non-humanized BCMA CAR-T failure. These findings support further investigation into retreatment strategies and post-CAR-T maintenance approaches.
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