复发性和难治性表达 CD30 的淋巴瘤需要新的治疗方法。我们开发了一种新型抗CD30 CAR，命名为5F11-28Z。在 I 期剂量递增临床试验中评估了 5F11-28Z 转导 T 细胞 (5F11-T) 的安全性和可行性。表达 CD30 的淋巴瘤患者在第 -5 至 -3 天接受 300 mg/m2 或 500 mg/m2 环磷酰胺和 30 mg/m2 氟达拉滨，随后在第 0 天输注 5F11-T。21 名患者接受 5F11- T输液。 20 名患者患有经典霍奇金淋巴瘤，1 名患者患有间变性大细胞淋巴瘤。患者接受了大量的预处理，中位接受过 7 次治疗，肿瘤负荷很大，中位代谢肿瘤体积 (MTV) 为 66.1 mL（范围 6.4 - 486.7 mL）。总体回应率为43%；一名患者获得完全缓解。中位无事件生存期为 13 周。 11 名患者患有细胞因子释放综合征（CRS；52%）。 1 名患者出现 3 级 CRS，无 4-5 级 CRS。神经系统毒性很小。九名患者（43%）出现新发皮疹。两名患者（9.5%）因长期严重皮疹而接受延长疗程的皮质类固醇治疗。 5 名患者 (24%) 出现 3-4 级血细胞减少，恢复时间为 30 天或更长，其中 2 名患者 (9.5%) 出现长期血细胞减少，病程并发危及生命的败血症。由于毒性，该试验提前停止。中位峰值血液 CAR 细胞/μL 为 26（范围 1-513），但淋巴结活检中未检测到 CAR 细胞浸润。 5F11-T功效低且毒性大，限制了5F11-T的进一步发展。 CT# NCT03049449。版权所有 © 2023 美国血液学会。

New treatments are needed for relapsed and refractory CD30-expressing lymphomas. We developed a novel anti-CD30 CAR, designated 5F11-28Z. Safety and feasibility of 5F11-28Z-transduced T cells (5F11-T) were evaluated in a phase I dose escalation clinical trial. Patients with CD30-expressing lymphomas received 300 mg/m2 or 500 mg/m2 of cyclophosphamide and 30 mg/m2 of fludarabine on days -5 to -3 followed by infusion of 5F11-T on day 0. Twenty-one patients received 5F11-T infusions. Twenty patients had Classical Hodgkin lymphoma, and 1 had anaplastic large cell lymphoma. Patients were heavily pretreated, with a median of 7 prior lines of therapy and substantial tumor burden, with a median metabolic tumor volume (MTV) of 66.1 mL (range 6.4 - 486.7 mL). The overall response rate was 43%; one patient achieved a complete remission. Median event-free survival was 13 weeks. Eleven patients had cytokine release syndrome (CRS; 52%). One patient had grade 3 CRS, and there was no grade 4-5 CRS. Neurologic toxicity was minimal. Nine patients (43%) had new onset rashes. Two patients (9.5%) received extended courses of corticosteroids for prolonged severe rashes. Five patients (24%) had grade 3-4 cytopenias with recovery time of 30 days or more, and 2 of these patients (9.5%) had prolonged cytopenias with courses complicated by life-threatening sepsis. The trial was halted early due to toxicity. Median peak blood CAR+ cells/µL was 26 (range 1-513), but no infiltration of CAR+ cells was detected in lymph node biopsies. 5F11-T had low efficacy and substantial toxicities, which limit further development of 5F11-T. CT# NCT03049449.Copyright © 2023 American Society of Hematology.