C-X-C Motif Chemokine Receptor 4-Targeted Radioligand Therapy in Patients with Advanced T-Cell Lymphoma
C-X-C Motif Chemokine Receptor 4-Targeted Radioligand Therapy in Patients with Advanced T-Cell Lymphoma
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DOI：
10.2967/jnumed.122.264207
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发表时间：
2023-01-01
影响因子：
9.3
通讯作者：
Werner, Rudolf A.
中科院分区：
文献类型：
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作者：
Buck, Andreas K.;Grigoleit, Goetz Ulrich;Werner, Rudolf A.
C-X-Cmotif 趋化因子受体 4 (CXCR4) 靶向放射配体疗法 (RLT) 已应用于晚期血癌，例如多发性骨髓瘤或弥漫性大 B 细胞淋巴瘤。我们介绍了一系列晚期 T 细胞淋巴瘤 (TCL) 患者，他们计划接受 CXCR4 定向治疗作为预处理方案，然后进行造血干细胞移植 (HSCT)。方法：四名晚期、经过大量治疗且复发的 TCL 患者（2 名男性，2 名女性；中位年龄，50 岁），没有合适的替代治疗选择，接受了 CXCR4 导向的 PET 和治疗前剂量测定。然后，我们结合同种异体（3/4，75%）或自体（1/4，25%）HSCT 进行了 CXCR4 靶向 RLT。一名患者还接受了针对 CD66 的放射免疫治疗，以增强治疗效果。我们研究了安全性、最佳反应、无进展生存期和总生存期。结果：治疗前剂量测定表明，CXCR4 靶向 RLT 的淋巴瘤吸收剂量高达 33.2 Gy。除 1 名患者出现肿瘤溶解综合征并伴有短暂性 3 级肾衰竭外，治疗期间未记录到急性毒性、过敏反应或其他不良事件。一名患者出现败血症，随后在 RLT 后 16 天死亡，而其余 3 名患者 (75%) 实现了植入。在随访期间，3 名患者中有 1 名 (33.3%) 出现部分缓解，另外两名 (66.7%) 出现完全代谢缓解，其中 1 名患者还接受了额外的放射免疫治疗。中位无进展生存期为 7 个月（范围：4-25 个月）。中位随访 54 个月（范围：4-56 个月）后，3 名患者在审查之日仍然活着。结论：对于晚期、经过大量预处理的 TCL，CXCR4 导向的 RLT 可能作为 HSCT 前的有效调理治疗，并可引起显着的抗淋巴瘤活性，从而在选定的病例中产生显着的反应。
C-X-Cmotif chemokine receptor 4 (CXCR4)-targeted radioligand therapy (RLT) has already been applied to advanced blood cancers, such as multiple myeloma or diffuse large B-cell lymphoma. We present a series of patients with advanced T-cell lymphoma (TCL) who were scheduled for CXCR4-directed therapy as a conditioning regimen, followed by hematopoietic stem cell transplantation (HSCT). Methods: Four patients with advanced, heavily pretreated, and relapsed TCL (2 men, 2 women; median age, 50 y) without suitable alternative therapeutic options underwent CXCR4-directed PET and pretherapeutic dosimetry. We then conducted CXCR4-targeted RLT in combination with allogeneic (3/4, 75%) or autologous (1/4, 25%) HSCT. One patient also underwent radioimmunotherapy targeting CD66 to enhance therapeutic efficacy. We investigated safety, best response, progression-free survival, and overall survival. Results: Pretherapeutic dosimetry indicated lymphoma-absorbed doses of up to 33.2 Gy from CXCR4-targeted RLT. Except for 1 patient who developed tumor lysis syndrome along with transient grade 3 kidney failure, no acute toxicity, allergic reactions, or other adverse events were recorded during therapy. One patient developed septicemia and subsequently died 16 d after RLT, whereas engraftment was achieved in the remaining 3 patients (75%). During follow-up, a partial response was recorded in 1 of 3 patients (33.3%) and a completemetabolic response in the other two (66.7%, with 1 patient also receiving additional radioimmunotherapy). Median progression-free survival was 7mo (range, 4-25mo). After a median follow-up of 54 mo (range, 4-56 mo), 3 patients were still alive at the date of censoring. Conclusion: For advanced, heavily pretreated TCL, CXCR4-directed RLTmay serve as an effective conditioning therapy before HSCT and can cause substantial antilymphoma activity, leading to a remarkable response in selected cases.