First-in-Human Experience of CXCR4-Directed Endoradiotherapy with 177Lu- and 90Y-Labeled Pentixather in Advanced-Stage Multiple Myeloma with Extensive Intra- and Extramedullary Disease

Chemokine receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer. Based on promising experiences with a radiolabeled CXCR4 ligand (Ga-68-pentixafor) for diagnostic receptor targeting, Lu-177- and Y-60-pentixather were recently developed as endoradiotherapeutic vectors. Here, we summarize the first-in-human experience in 3 heavily pretreated patients with intramedullary and extensive extramedullary manifestations of multiple myeloma undergoing CXCR4-directed endoradiotherapy. Methods: CXCR4 target expression was demonstrated by baseline Ga-68-pentixafor PET. Each treatment was approved by the clinical ethics committee. Pretherapeutic Lu-177-pentixather dosimetry was performed before Lu-177-pentixather or Y-60-pentixather treatment. Subsequently, patients underwent additional chemotherapy and autologous stem cell transplantation for bone marrow rescue. Results: A remarkable therapeutic effect was visualized in 2 patients, who showed a significant reduction in F-18-FDG uptake. Conclusion: CXCR4-targeted radiotherapy with pentixather appears to be a promising novel treatment option in combination with cytotoxic chemotherapy and autologous stern cell transplantation, especially for patients with advanced multiple myeloma.