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 (68Ga-pentixafor) for diagnostic receptor targeting, ¹⁷⁷Lu-and 90Y-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 68Ga-pentixafor PET. Each treatment was approved by the clinical ethics committee. Pretherapeutic ¹⁷⁷Lu-pentixather dosimetry was performed before ¹⁷⁷Lu-pentixather or 90Y-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 ¹⁸F-FDG uptake. Conclusion: CXCR4-targeted radiotherapy with pentixather appears to be a promising novel treatment option in combination with cytotoxic chemotherapy and autologous stem cell transplantation, especially for patients with advanced multiple myeloma.