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

Abstract

<b>Objectives:</b> C-X-C motif 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 herein present a series of patients with advanced T-cell lymphoma (TCL), who were scheduled for CXCR4-directed therapy as conditioning regimen, followed by hematopoietic stem cell transplantation (HSCT). <b>Methods:</b> Four patients with advanced, heavily pretreated and relapsed TCL (2 males, 2 females; median age, 50 years) 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 (PFS) and overall survival. <b>Results:</b> Pretherapeutic dosimetry indicated lymphoma absorbed doses of up to 33.2 Gy from CXCR4-targeted RLT. Except for one patient developing 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 days after RLT, while engraftment was achieved in the remaining 3 subjects (75%). During follow-up, partial response was recorded in 1 patient (33.3%) and complete metabolic response in 2/3 (66.7%, with one patient also receiving additional radioimmunotherapy). Median PFS was 7 months (range, 4 – 25 m). After a median follow-up of 54 m (range, 4 – 56 m), three patients were still alive at date of censoring. <b>Conclusion:</b> For advanced, heavily pretreated TCL, CXCR4-directed RLT may serve as an effective conditioning therapy prior to HSCT and can cause substantial anti-lymphoma activity, leading to remarkable response in selected cases.