4.7 Article

C-X-C Motif Chemokine Receptor 4-Targeted Radioligand Therapy in Patients with Advanced T-Cell Lymphoma

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JOURNAL OF NUCLEAR MEDICINE
卷 64, 期 1, 页码 34-39

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SOC NUCLEAR MEDICINE INC
DOI: 10.2967/jnumed.122.264207

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C-X-C motif chemokine receptor 4; CXCR4; chemokine receptor; theranostics; radioligand therapy; T-cell lymphoma

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In this study, we investigated the use of CXCR4-targeted radioligand therapy (RLT) as a conditioning regimen for hematopoietic stem cell transplantation (HSCT) in patients with advanced T-cell lymphoma. The results showed that CXCR4-directed RLT can be an effective treatment option, leading to remarkable antilymphoma activity in selected cases.
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.

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