Conflict of interest: R. Vij was an investigator in this study.
Article first published online: 25 JUL 2009
Copyright © 2009 Wiley-Liss, Inc.
American Journal of Hematology
Volume 84, Issue 10, pages 650–656, October 2009
How to Cite
Vij, R., Horvath, N., Spencer, A., Taylor, K., Vadhan-Raj, S., Vescio, R., Smith, J., Qian, Y., Yeh, H. and Jun, S. (2009), An open-label, phase 2 trial of denosumab in the treatment of relapsed or plateau-phase multiple myeloma. Am. J. Hematol., 84: 650–656. doi: 10.1002/ajh.21509
Disclosures: R. Vij, MD; A. Spencer, MBBS, FRACP, FRCPA, DM; K. Taylor, MD; and R. Vescio, MD were investigators in this study and have no other relevant conflicts of interest to disclose. S. Vadhan-Raj, MD has received research funding from Amgen Inc. for clinical studies and an honorarium as a speaker for Amgen Inc. N. Horvath, MD received research funding from Amgen Inc. and was an investigator in this study. J. Smith, BA, Y.Qian, PhD, S. Jun, MD, and H. Yeh, MD are Amgen Inc. employees and have received stocks/stock options from Amgen Inc.
- Issue published online: 25 SEP 2009
- Article first published online: 25 JUL 2009
- Accepted manuscript online: 25 JUL 2009 12:00AM EST
- Manuscript Accepted: 18 JUL 2009
- Manuscript Revised: 14 JUL 2009
- Manuscript Received: 31 MAR 2009
- Amgen Inc., Thousand Oaks, CA
RANKL is a key mediator of osteoclast differentiation, activation, and survival. Preclinical data suggest that aberrant production and activation of osteoclasts may influence proliferation of multiple myeloma (MM) cells in the bone marrow. Reports have also shown that inhibiting RANKL may have a direct effect on RANK-expressing myeloma cells and a therapeutic role in treating the disease. In mouse myeloma models, inhibition of RANKL led to reduced serum paraprotein levels and tumor burden. Based on this hypothesis, this proof-of-concept, single-arm study investigated whether RANKL inhibition with denosumab could reduce serum M-protein levels in relapsed or plateau-phase myeloma subjects. All subjects received denosumab monthly, with loading doses on days 8 and 15 of month one, until disease progression or subject discontinuation. Results of this ongoing study demonstrated that no subjects in either cohort met the protocol-defined objective response criteria of complete response (CR) or partial response (PR), but that denosumab effectively inhibited the RANKL pathway regardless of previous exposure to bisphosphonates, as evidenced by suppressed levels of the bone turnover marker, serum C-terminal telopeptide of type 1 collagen (sCTx). Eleven (21%) subjects who relapsed within 3 months before study entry maintained stable disease for up to 16.5 months. Nineteen (46%) subjects with plateau-phase myeloma maintained stable disease for up to 18.3 months. The adverse event (AE) profile for denosumab and its dosing schedule in these populations was consistent with that for advanced cancer patients receiving systemic therapy. Additional controlled clinical studies of denosumab in subjects with both relapsed and plateau-phase MM are warranted. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc.