First-in-Human Experience of CXCR4-Directed Endoradiotherapy with sigma up 177 Lambda u- and sigma up 90 Xi -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-pentixafor) for diagnostic receptor targeting, ...Lu- and ...Y-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. CXCR4 target expression was demonstrated by baseline ...Ga-pentixafor PET. Each treatment was approved by the clinical ethics committee. Pretherapeutic ...Lu-pentixather dosimetry was performed before ...Lu-pentixather or ...Y-pentixather treatment. Subsequently, patients underwent additional chemotherapy and autologous stem cell transplantation for bone marrow rescue. A remarkable therapeutic effect was visualized in 2 patients, who showed a significant reduction in ...F-FDG uptake. 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. (ProQuest: ... denotes formulae/symbols omitted.)