CXCR4-Directed Endoradiotherapy as New Treatment Option in Advanced Multiple Myeloma

Abstract

Multiple myeloma (MM) accounts for approximately 1% of all cancers and around 10% of hematological malignancies. Although various novel drugs and treatment options including proteasome inhibitors, immunomodulators, antibodies, or the implementation of autologous and allogeneic stem cell transplantation have improved overall survival over the last decades, MM essentially remains an incurable disease. In relapsed/refractory disease, even the most intense treatment regimens frequently fail to efficiently reduce the tumor burden, and patients eventually succumb to their disease. Given the paramount importance of C-X-C chemokine receptor CXCR4 for both multiple myeloma and bone marrow microenvironment, development of radiolabeled receptor ligands for both CXCR4-directed imaging and therapy has opened new exciting opportunities in the field of radionuclide therapies. Endoradiotherapy can be safely performed as part of the conditioning regimen prior to autologous or allogeneic stem cell transplantation. First experience has hinted at high tumor cell kill in even very advanced MM including extramedullary disease. Further prospective studies to evaluate the efficacy in earlier disease stages are about to be initiated and will also provide further evidence on synergistic multimodality treatment.