1553TiP - Comparison of denosumab vs zoledronic acid for treatment of bone disease in adults with newly diagnosed multiple myeloma: A randomized, double-blin...

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Supportive Measures
Plasma Cell Dyscrasias
Presenter Evangelos Terpos
Citation Annals of Oncology (2014) 25 (suppl_4): iv517-iv541. 10.1093/annonc/mdu356
Authors E. Terpos1, N. Raje2, B.G. Durie3, R. Garcia-Sanz4, K. Shimizu5, W. Willenbacher6, L. Zhu7, A. Braun8, R. Jain9, A. Palumbo10
  • 1Department Of Clinical Therapeutics, University of Athens School of Medicine, Alexandra General Hospital, 11528 - Athens/GR
  • 2Center For Multiple Myeloma, Massachusetts General Hospital Cancer Center, Boston/US
  • 3Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Outpatient Cancer Center, 90048 - Los Angeles/US
  • 4Department Of Hematology, University Hospital of Salamanca, 37007 - Salamanca/ES
  • 5Department Of Hematology, Tokai Chuo Hospital, Kakamigahara City/JP
  • 6Hematology And Oncology, Medical University of Innsbruck, Innsbruck/AT
  • 7Global Biostatistical Science, Amgen, 91320 - Thousand Oaks/US
  • 8Global Development, Amgen, 91320 - Thousand Oaks/US
  • 9Global Development, Amgen Inc., Thousand Oaks/US
  • 10Myeloma Unit, University of Turin, IT-10126 - Torino/IT



A characteristic feature of multiple myeloma (MM) is bone destruction mediated by osteoclasts. This breakdown of bone releases factors that mediate myeloma cell growth, creating a cycle of skeletal damage and tumor cell growth. Patients with MM and bone lesions can experience debilitating pain and skeletal complications including pathologic fractures, need for radiotherapy or surgery to bone, and spinal cord compression, collectively termed skeletal-related events (SREs). RANKL is the key mediator of osteoclast activity. Denosumab, a fully human monoclonal antibody specific to RANKL, inhibits the formation, function, and survival of osteoclasts, thus decreasing cancer-mediated bone destruction. The primary endpoint of this trial is to determine whether denosumab is noninferior to zoledronic acid (ZA) in delaying the time to 1st on-study SRE in patients with MM. Secondary endpoints include superiority of denosumab vs ZA in delaying the time to 1st on-study SRE and time to 1st-and-subsequent SRE and overall survival. Safety endpoints will be assessed. This trial is registered (ClinicalTrials.gov NCT01345019) and sponsored by Amgen Inc.

Trial design

We are targeting enrollment of ∼1520 adults with newly diagnosed MM and ≥1 bone lesion. Patients with ≤30 days of anti-myeloma therapy, ≤1 prior dose of IV bisphosphonate, an ECOG status ≤2, and adequate organ function are eligible. Use of any approved treatment regimen is permitted as anti-myeloma treatment in this trial. Enrolled patients are stratified by whether they intend to undergo autologous stem cell transplant; use of novel vs non-novel anti-myeloma agents as 1st-line therapy; stage at diagnosis per the International Staging System; SRE at time of presentation; and geographic region. Randomized (1:1) patients receive either SC denosumab 120 mg+IV placebo or IV ZA 4 mg (adjusted for CrCl)+SC placebo once every 4 weeks. Daily calcium (≥500 mg) and vitamin D (≥400 IU) supplements are strongly recommended. The primary analysis is planned when ∼800 patients experience an on-study SRE. Enrollment is currently ongoing and enrollment rates are as planned. Reused with permission from the American Society of Clinical Oncology (ASCO). This abstract was accepted and previously presented at the 2014 ASCO Annual Meeting (TPS8628). All rights reserved.


E. Terpos: Consultant for Amgen, Janssen-Cilag, and Morphosys; Honoraria from Celgene and Novartis; N. Raje: Consultant for Amgen; R. Garcia-Sanz: Honoraria from Amgen; Research funding from Novartis; K. Shimizu: Consultant for and honoraria and research funding from Daiichi Sankyo; Expert testimony on behalf of Amgen; W. Willenbacher: Consultant for and honoraria and research funding from Amgen; L. Zhu: Employee of Amgen; Own stock or stock options in Amgen; A. Braun: Previous employee of Amgen; Own stock or stock options in Amgen; R. Jain: Employee of Amgen; Own stock or stock options in Amgen; A. Palumbo: Consultant for and honoraria from Amgen, Bristol-Myers Squibb, Celgene, Janssen, Millenium, and Onyx. All other authors have declared no conflicts of interest.