Denosumab Versus Zoledronic Acid in Bone Disease Treatment of Newly Diagnosed Multiple Myeloma: An International, Double-Blind, Randomized Controlled Phase 3 Study-Asian Subgroup Analysis

Shang-Yi Huang, Sung-Soo Yoon, Kazuyuki Shimizu, Wee Joo Chng, Cheng-Shyong Chang, Raymond Siu-Ming Wong, Seasea Gao, Yang Wang, Steve W Gordon, Anthony Glennane, Chang-Ki Min, Shang-Yi Huang, Sung-Soo Yoon, Kazuyuki Shimizu, Wee Joo Chng, Cheng-Shyong Chang, Raymond Siu-Ming Wong, Seasea Gao, Yang Wang, Steve W Gordon, Anthony Glennane, Chang-Ki Min

Abstract

Introduction: The primary analysis of a global phase 3 study that evaluated the efficacy and safety of denosumab versus zoledronic acid for preventing skeletal-related events (SREs) in adults with newly diagnosed multiple myeloma (MM) indicated that denosumab was noninferior to zoledronic acid for time to first on-study SREs. Here we present a subgroup analysis to evaluate efficacy and safety in Asian patients.

Methods: Patients were randomized 1:1 to receive denosumab 120 mg subcutaneously or zoledronic acid intravenously 4 mg every 4 weeks in a double-blind, double-dummy fashion. All patients received standard-of-care first-line antimyeloma treatment. Each patient received either study drug until an estimated 676 patients experienced at least one on-study SRE and the primary efficacy and safety analyses were completed.

Results: Of 1718 total enrolled patients, 196 Asian patients (denosumab, n = 103; zoledronic acid, n = 93) were included in this subgroup analysis. Fewer patients in the denosumab group developed first on-study SRE compared with the zoledronic acid group; the crude incidence of SREs at the primary analysis cutoff was 38.8% and 50.5%, respectively (HR [95% CI], 0.77 [0.48-1.26]). All 194 patients receiving at least one dose of study drug experienced at least one treatment-emergent AE. The most common AEs reported in either group (denosumab, zoledronic acid) were diarrhea (51.0%, 51.1%), nausea (42.2%, 46.7%), and pyrexia (38.2%, 41.3%). Treatment-emergent renal toxicity occurred in 9/102 (8.8%) and 20/92 (21.7%) patients, respectively. Similar rates of positively adjudicated osteonecrosis of the jaw (7 [6.9%] vs 5 [5.4%]) and treatment-emergent hypocalcemia (19 [18.6%] vs 17 [18.5%]) were reported in the denosumab and zoledronic acid groups, respectively.

Conclusion: Efficacy and safety outcomes from this Asian subgroup were comparable to those of the full study population. Overall, this analysis supports denosumab as an additional treatment option for standard of care for Asian patients with newly diagnosed MM with lytic bone lesions.

Clinical trial registration: ClinicalTrials.gov NCT01345019.

Keywords: Asian patients; Denosumab; Multiple myeloma; Skeletal-related event; Zoledronic acid.

Figures

Fig. 1
Fig. 1
Study design and treatment schema. ASCT autologous stem cell transplant, ISS International Staging System, IV intravenously administered, Q4W every 4 weeks, SC subcutaneously administered, SRE skeletal-related event
Fig. 2
Fig. 2
Time to first on-study SRE for Asian subgroup. CI confidence interval, HR hazard ratio, N number of patients randomized in Asian subgroup, Q4W every 4 weeks, SRE skeletal-related event. HR < 1 favors denosumab
Fig. 3
Fig. 3
Progression-free survival for Asian subgroup. CI confidence interval, HR hazard ratio, N number of patients randomized in Asian subgroup, Q4W every 4 weeks. HR < 1 favors denosumab

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Source: PubMed

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