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

Andreas K. Buck, Götz Ulrich Grigoleit, Sabrina Kraus, Andreas Schirbel, Michael Heinsch, Niklas Dreher, Takahiro Higuchi, Constantin Lapa, Heribert Hänscheid, Samuel Samnick, Hermann Einsele, Sebastian E. Serfling, Rudolf A. Werner

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


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 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 complete metabolic response in the other two (66.7%, with 1 patient also receiving additional radioimmunotherapy). Median progression-free survival was 7 mo (range, 4-25 mo). 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 RLT may serve as an effective conditioning therapy before HSCT and can cause substantial antilymphoma activity, leading to a remarkable response in selected cases.

Original languageEnglish
Pages (from-to)34-39
Number of pages6
JournalJournal of Nuclear Medicine
Issue number1
Publication statusPublished - Jan 1 2023
Externally publishedYes


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

ASJC Scopus subject areas

  • Medicine(all)


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