肿瘤细胞治疗研究
英文原题：Autologous stem cell transplantation in tandem with Anti-CD30 CAR T-cell infusion in relapsed/refractory CD30(+) lymphoma.
我们的工作表明，ASCT联合CAR30 T细胞治疗在r/r cHL和ALCL中耐受性良好且高度有效，即使在预期ASCT后预后较差的PET阳性或化疗难治性患者中也是如此，尽管仍需在前瞻性临床试验中进行进一步大规模验证。试验注册 该试验已在中国临床试验注册中心注册（ChiCTR，注册号ChiCTR2100053662）。
对于对挽救化疗耐药的复发/难治性（r/r）淋巴瘤患者，即使随后进行自体干细胞移植（ASCT），长期结局也不佳。尽管抗CD30嵌合抗原受体（CAR30）T细胞疗法在这些患者中诱导了较高的缓解率，但缓解持续时间相对有限。
这项开放标签、单中心、单臂初步研究探讨了ASCT联合CAR30 T细胞输注治疗r/r CD30+淋巴瘤的安全性和疗效。主要终点为安全性，关键次要终点为总缓解率、总生存期、无进展生存期和缓解持续时间。
5例经典霍奇金淋巴瘤（cHL）患者和1例间变性淋巴瘤激酶（ALK）阴性间变性大细胞淋巴瘤（ALCL）患者被纳入研究。中位年龄为24岁。无患者既往接受过ASCT。3例患者（50.0%）复发2次，3例患者（50.0%）患有原发难治性疾病。所有患者的Deauville评分均为4或5分，5例患者（83.3%）在入组时疾病稳定或进展（SD/PD）。所有患者均接受了清髓性化疗，并序贯输注CD34阳性造血干细胞（HSCs）和CAR30 T细胞，中位剂量分别为3.9 × 10^6/kg和7.6 × 10^6/kg。5例患者出现细胞因子释放综合征（CRS），均为1级。未观察到神经毒性。所有患者均成功植入HSCs并达到客观缓解，其中5例（4例cHL和1例ALCL，83.3%）达到完全缓解（CR），1例达到部分缓解（PR）。中位随访时间为20.4个月（范围12.1-34.4个月），所有患者均存活并维持缓解。
BACKGROUND: Long-term outcome is unfavourable for relapsed/refractory (r/r) lymphoma patients who are resistant to salvage chemotherapy, even after subsequent autologous stem-cell transplantation (ASCT). Although anti-CD30 chimeric antigen receptor (CAR30) T-cell therapy induces high response rates in these patients, the duration of response is relatively limited. METHODS: This open-label, single-center and single-arm pilot study investigated the safety and efficacy of ASCT in tandem with CAR30 T-cell infusion in r/r CD30 + lymphoma. The primary endpoint was safety and key secondary endpoint was overall response rate, overall survival, progression-free survival, and duration of response. RESULTS: Five classical Hodgkin lymphoma (cHL) patients and 1 anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL) patient were enrolled. The median age was 24 years. No patient had prior ASCT. Three patients (50.0%) relapsed for 2 times and 3 patients (50.0%) had primary refractory diseases. All had a Deauville score of 4 or 5, and 5 patients (83.3%) had a stable or progressive disease (SD/PD) at enrollment. All patients received myeloablative chemotherapy and infused CD34-positive hematopoietic stem cells (HSCs) and CAR30 T cells in tandem, with a median dose of 3.9 10 6 /kg and 7.6 10 6 /kg, respectively. Five paitents presented with cytokine release syndrome (CRS), all of which were grade 1. No neurotoxicity was observed. All patients had successful HSCs engraftment and reached an objective response, including 5 (4 cHL and 1 ALCL, 83.3%) with a complete response (CR) and 1 with a partial response (PR). With a median follow-up of 20.4 (range, 12.1-34.4) months, all remained alive and maintained their responses. CONCLUSION: Our work demonstrates the combined administration of ASCT and CAR30 T-cell therapy is well-tolerate and highly effective in r/r cHL and ALCL, even in PET-positive or chemorefractory patients who are expected to have inferior outcome after ASCT, although further large-scaled validation in prospective clinical trial is warranted. Trial registration The trial was registered with the Chinese Clinical Trial Registry (ChiCTR, number ChiCTR2100053662).
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