肿瘤细胞治疗研究
英文原题：Long-term follow-up results of anti-BCMA CAR-T cell therapy combined with autologous hematopoietic stem cell transplantation in relapsed/refractory multiple myeloma with extramedullary disease.
我们回顾性总结了 3 年随访的结果，发现抗 BCMA CAR-T 细胞疗法与 auto-HSCT 联合与伴 EMD 的 R/R MM 患者 PFS 和 OS 改善相关。
背景：伴髓外病变（EMD）的复发/难治性多发性骨髓瘤（R/R MM）预后较差。目前治疗包括自体造血干细胞移植（auto-HSCT）和嵌合抗原受体（CAR）T细胞疗法，但应答仍不理想；即使初始应答，早期进展也较常见。本研究旨在评估CAR T细胞治疗联合auto-HSCT这一治疗策略的疗效。 方法：18例伴EMD的R/R MM患者参加抗BCMA CAR-T临床试验。其中8例接受CAR-T联合auto-ASCT（T-C组），其余10例仅接受CAR T细胞治疗（C组）。我们回顾性比较两组的临床应答、CAR T细胞扩增动力学、T细胞亚群特征、血清白细胞介素6（IL-6）水平、治疗相关毒性及长期结局。 结果：根据血液学和影像学综合评估EMD，T-C组8例患者均达到总体缓解（ORR）。相比之下，C组10例中有8例符合血液学ORR标准，但仅6例EMD病灶显示影像学应答。T-C组无进展生存期（PFS）和总生存期（OS）明显改善。该组CAR-T细胞和IL-6的峰值水平均更高。输注后第28天，T-C组CD3+ CD4+ T细胞比例显著较高。尽管T-C组细胞因子释放综合征（CRS）趋于更严重，两组免疫效应细胞相关神经毒性综合征（ICANS）的发生率和严重程度相当。T-C组血液学恢复延迟，8例中有3例发生移植物功能不良。 结论：我们回顾性总结了3年随访结果，发现抗BCMA CAR-T细胞疗法联合auto-HSCT与伴EMD的R/R MM患者PFS和OS改善相关。此外，CD4 T细胞动态变化可能与T-C组观察到的持久临床应答相关。尽管T-C组发生了更高级别CRS和较持久的血液学毒性，但未观察到由治疗相关毒性导致的死亡。（试验注册号：ChiCTR2000033925。）试验注册：注册机构为天津市第一中心医院。 试验注册号：ChiCTR2000033925。注册日期：2020年6月17日。患者依据《赫尔辛基宣言》签署书面知情同意，并同意将其数据用于本研究。
BACKGROUND: Relapsed/refractory multiple myeloma (R/R MM) with extramedullary disease (EMD) has a poor prognosis. Responses to current therapies, including autologous hematopoietic stem cell transplantation (auto-HSCT) and chimeric antigen receptor (CAR) T-cell therapy, remain unsatisfactory or show frequent early progression despite an initial response. In this study, we aimed to investigate the efficacy of a therapeutic approach combining CAR T-therapy with auto-HSCT. METHODS: Eighteen patients with R/R MM with EMD were enrolled in clinical trials evaluating anti-BCMA CAR-T therapy. Of these, eight patients were treated in combination with auto-ASCT in combination (T-C group), while the remaining ten underwent CAR T-cell therapy alone (C group). We retrospectively compared the clinical responses, CAR T-cell expansion kinetics, T-cell subset profiles, serum interleukin-6 (IL-6) levels, treatment-related toxicities, and long-term outcomes between the two cohorts. RESULTS: In the T-C group, all 8 patients achieved an overall response (ORR) (ORR) based on the combined haematologic and imaging assessments of EMD. In contrast, among the 10 patients in the C group, 8 met the haematologic criteria for ORR, but only 6 demonstrated a radiographic response in EMD lesions. Progression-free survival (PFS) and overall survival (OS) were markedly improved in the T-C group. This cohort also exhibited higher peak levels of both CAR- T cells and IL-6. On day 28 post-infusion, the proportion of CD3 CD4 T cells was significantly higher in the T-C group. While cytokine release syndrome (CRS) tended to be more severe in this group, the incidence and severity of the immune effector cell-associated neurotoxicity syndrome (ICANS) was comparable between the two groups. Haematologic recovery was delayed in the T-C group, and three of the eight patients developed poor graft function. CONCLUSION: We retrospectively summarised the results of a 3-year follow-up and found that the combination of anti-BCMA CAR-T cell therapy and auto-HSCT was associated with improved PFS and OS in R/R MM patients with EMD. Moreover, CD4 T-cell dynamics may be associated with the durable clinical response observed in the T-C group. Although the T-C group experienced higher-grade CRS and prolonged haematological toxicity, no treatment-related deaths due to treatment-related toxicities were observed. (Trial registration: ChiCTR2000033925). TRIAL REGISTRATION: Registration center: Tianjin First Central Hospital. TRIAL REGISTRATION NUMBER: ChiCTR2000033925. Registration Date: June 17, 2020. The patient gave their written informed consent in accordance with the Declaration of Helsinki. The patients agreed to have their data used in our study.
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