Denosumab in multiple myeloma patients with severe renal impairment: a multicenter phase 2 study
Lytic bone lesions are a defining characteristic of multiple myeloma (MM) and one of its most significant clinical consequences. Bone-modifying agents, including the bisphosphonates zoledronic acid and pamidronate, as well as the receptor activator of nuclear factor-κB ligand (RANKL) monoclonal antibody denosumab, are a mainstay of bone supportive care [ 1 , 2 ]. However, a major limitation of zoledronic acid and pamidronate is nephrotoxicity, with guidelines recommending caution in patients with creatinine clearance <30 mL/min [ 3 ]. This is particularly relevant in MM where renal dysfunction is common at presentation and at relapse [ 4 ]. In contrast, denosumab has a significantly lower risk of kidney injury compared with zoledronic acid in a large, randomized study in MM that led to its approval [ 5 ]. However, patients with creatinine clearance <30 mL/min were excluded from this trial, limiting application of these findings to this subgroup. Given the unmet need for bone supportive care in MM patients with renal impairment, we conducted a prospective, multicenter, phase 2 trial of denosumab in this patient population (NCT02833610).
Authors
- Robert Allyn Redd (ORCID: https://orcid.org/0000-0002-1329-5288)
- Ajay K. Nooka (ORCID: https://orcid.org/0000-0003-4165-6869)
- Andrew Robert Branagan (ORCID: https://orcid.org/0000-0002-3868-9267)
- Paul Gerard Guy Richardson (ORCID: https://orcid.org/0000-0002-7426-8865)
- Jacob P. Laubach (ORCID: https://orcid.org/0000-0001-7565-2052)
- Noopur S Raje (ORCID: https://orcid.org/0000-0003-3066-1275)
- Omar Nadeem (ORCID: https://orcid.org/0000-0002-4124-4277)
- Andrew Jenho Yee (ORCID: https://orcid.org/0000-0003-3623-7491)
- Elizabeth O’Donnell (ORCID: https://orcid.org/0000-0002-4042-1526)
- Ehsan Malek (ORCID: https://orcid.org/0000-0003-4719-4327)
- Giada Bianchi (ORCID: https://orcid.org/0000-0003-3673-0104)
- Brea C. Lipe (ORCID: https://orcid.org/0000-0002-7596-2015)
- Robb S. Friedman
Institutions
- Roswell Park Comprehensive Cancer Center (US)
- Harvard University (US)
- Emory University (US)
- University Hospitals of Cleveland (US)
- Newton Wellesley Hospital (US)
- University of Rochester Medical Center (US)
- South Shore Hospital (US)
- Dana-Farber Cancer Institute (US)
- Dana-Farber Brigham Cancer Center (US)
- Winship Cancer Institute (US)
- Mass General Brigham (US)
- University of Rochester (US)
Publication Details
- Journal
- Blood Cancer Journal
- Published
- 2026-11-02
- DOI
- https://doi.org/10.1038/s41408-026-01656-y
- Primary Topic
- Bone health and treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Amgen