CXCR4-directed endoradiotherapy induces high response rates in extramedullary relapsed Multiple Myeloma

• Published in: Theranostics 2017-01, Vol.7 (6), p.1589-1597
• Main Authors: Lapa, Constantin, Herrmann, Ken, Schirbel, Andreas, Hänscheid, Heribert, Lückerath, Katharina, Schottelius, Margret, Kircher, Malte, Werner, Rudolf A, Schreder, Martin, Samnick, Samuel, Kropf, Saskia, Knop, Stefan, Buck, Andreas K, Einsele, Hermann, Wester, Hans-Juergen, Kortüm, K Martin
• Format: Article
• Language: English
• Subjects: Aged; Drug Therapy - methods; Female; Humans; Male; Middle Aged; Multiple Myeloma - therapy; Radiotherapy - methods; Receptors, CXCR4 - metabolism; Recurrence; Research Paper; Stem Cell Transplantation; Survival; Treatment Outcome
• ISSN: 1838-7640; 1838-7640
• DOI: 10.7150/thno.19050

C-X-C-motif chemokine receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer. We have recently reported promising first-in-man experience with CXCR4-directed endoradiotherapy (ERT) in multiple myeloma (MM). Eight heavily pretreated MM patients underwent a total of 10 ERT cycles (7 patients with 1 cycle and a single patient with 3 cycles). ERT was administered in combination with chemotherapy and autologous stem cell support. End points were occurrence and timing of adverse events, progression-free and overall survival. ERT was overall well tolerated without any unexpected acute adverse events or changes in vital signs. With absorbed tumor doses >30-70 Gy in intra- or extramedullary lesions, significant anti-myeloma activity was observed with 1 patient achieving complete remission and 5/8 partial remission. Directly after ERT major infectious complications were seen in one patient who died from sepsis 22 days after ERT, another patient with high tumor burden experienced lethal tumor lysis syndrome. Median progression-free survival was 54 days (range, 13-175), median overall survival was 223 days (range, 13-313). During follow-up (6 patients available), one patient died from infectious complications, 2/8 from disease progression, the remaining 3/8 patients are still alive. CXCR4-directed ERT was well-tolerated and exerted anti-myeloma activity even at very advanced stage MM with presence of extramedullary disease. Further assessment of this novel treatment option is highly warranted.