Denosumab for treatment of hypercalcemia of malignancy

Mimi I. Hu, Ilya G. Glezerman, Sophie Leboulleux, Karl Insogna, Rasim A. Gucalp, Waldemar Misiorowski, Bennett Yu, Paul Zorsky, Diego Tosi, Alberto Bessudo, Arnaud Jaccard, Giuseppe Tonini, Wendy Ying, Ada Braun, Rajul K. Jain

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Context: Hypercalcemia of malignancy (HCM) in patients with advanced cancer is often caused by excessive osteoclast-mediated bone resorption. Patients may not respond to or may relapse after iv bisphosphonate therapy. Copyright

Objective: We investigated whether denosumab, a potent inhibitor of osteoclast-mediated bone resorption, reduces serum calcium in patients with bisphosphonate-refractory HCM. Design, Setting, and Participants: In this single-arm international study, participants had serum calcium levels corrected for albumin (CSC) >12.5 mg/dL (3.1 mmol/L) despite bisphosphonates given >7 and ≤30 days before screening.

Intervention: Patients received 120 mg sc denosumab on days 1, 8, 15, and 29 and then every 4 weeks.

Main Outcome Measures: The primary endpoint was the proportion of patients with CSC ≤11.5 mg/dL (2.9 mmol/L) (response) by day 10. Secondary endpoints included response by visit, duration of response, and the proportion of patients with a complete response (CSC ≤10.8 mg/dL [2.7 mmol/L]) by day 10 and during the study.

Results: Patients (N = 33) had solid tumors or hematologic malignancies. By day 10, 21 patients (64%) reachedCSC≤11.5 mg/dL,and12 patients (33%) reachedCSC≤10.8 mg/dL. During the study, 23 patients (70%) reached CSC ≤11.5 mg/dL, and 21 patients (64%) reached CSC ≤10.8 mg/dL. Estimated median response duration was 104 days. The most common serious adverse events were hypercalcemia worsening (5 patients, 15%) and dyspnea (3 patients, 9%).

Conclusions: In patients with HCM despite recent iv bisphosphonate treatment, denosumab lowered serum calcium in64%of patients within 10 days, inducing durable responses.Denosumabmay offer a new treatment option for HCM.

Original languageEnglish (US)
Pages (from-to)3144-3152
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume99
Issue number9
DOIs
StatePublished - Sep 1 2014

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Diphosphonates
Hypercalcemia
Calcium
Neoplasms
Bone
Therapeutics
Refractory materials
Tumors
Albumins
Screening
Denosumab
Osteoclasts
Bone Resorption
Serum
Hematologic Neoplasms
Dyspnea

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

Cite this

Hu, M. I., Glezerman, I. G., Leboulleux, S., Insogna, K., Gucalp, R. A., Misiorowski, W., ... Jain, R. K. (2014). Denosumab for treatment of hypercalcemia of malignancy. Journal of Clinical Endocrinology and Metabolism, 99(9), 3144-3152. https://doi.org/10.1210/jc.2014-1001

Denosumab for treatment of hypercalcemia of malignancy. / Hu, Mimi I.; Glezerman, Ilya G.; Leboulleux, Sophie; Insogna, Karl; Gucalp, Rasim A.; Misiorowski, Waldemar; Yu, Bennett; Zorsky, Paul; Tosi, Diego; Bessudo, Alberto; Jaccard, Arnaud; Tonini, Giuseppe; Ying, Wendy; Braun, Ada; Jain, Rajul K.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 99, No. 9, 01.09.2014, p. 3144-3152.

Research output: Contribution to journalArticle

Hu, MI, Glezerman, IG, Leboulleux, S, Insogna, K, Gucalp, RA, Misiorowski, W, Yu, B, Zorsky, P, Tosi, D, Bessudo, A, Jaccard, A, Tonini, G, Ying, W, Braun, A & Jain, RK 2014, 'Denosumab for treatment of hypercalcemia of malignancy', Journal of Clinical Endocrinology and Metabolism, vol. 99, no. 9, pp. 3144-3152. https://doi.org/10.1210/jc.2014-1001
Hu, Mimi I. ; Glezerman, Ilya G. ; Leboulleux, Sophie ; Insogna, Karl ; Gucalp, Rasim A. ; Misiorowski, Waldemar ; Yu, Bennett ; Zorsky, Paul ; Tosi, Diego ; Bessudo, Alberto ; Jaccard, Arnaud ; Tonini, Giuseppe ; Ying, Wendy ; Braun, Ada ; Jain, Rajul K. / Denosumab for treatment of hypercalcemia of malignancy. In: Journal of Clinical Endocrinology and Metabolism. 2014 ; Vol. 99, No. 9. pp. 3144-3152.
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abstract = "Context: Hypercalcemia of malignancy (HCM) in patients with advanced cancer is often caused by excessive osteoclast-mediated bone resorption. Patients may not respond to or may relapse after iv bisphosphonate therapy. CopyrightObjective: We investigated whether denosumab, a potent inhibitor of osteoclast-mediated bone resorption, reduces serum calcium in patients with bisphosphonate-refractory HCM. Design, Setting, and Participants: In this single-arm international study, participants had serum calcium levels corrected for albumin (CSC) >12.5 mg/dL (3.1 mmol/L) despite bisphosphonates given >7 and ≤30 days before screening.Intervention: Patients received 120 mg sc denosumab on days 1, 8, 15, and 29 and then every 4 weeks.Main Outcome Measures: The primary endpoint was the proportion of patients with CSC ≤11.5 mg/dL (2.9 mmol/L) (response) by day 10. Secondary endpoints included response by visit, duration of response, and the proportion of patients with a complete response (CSC ≤10.8 mg/dL [2.7 mmol/L]) by day 10 and during the study.Results: Patients (N = 33) had solid tumors or hematologic malignancies. By day 10, 21 patients (64{\%}) reachedCSC≤11.5 mg/dL,and12 patients (33{\%}) reachedCSC≤10.8 mg/dL. During the study, 23 patients (70{\%}) reached CSC ≤11.5 mg/dL, and 21 patients (64{\%}) reached CSC ≤10.8 mg/dL. Estimated median response duration was 104 days. The most common serious adverse events were hypercalcemia worsening (5 patients, 15{\%}) and dyspnea (3 patients, 9{\%}).Conclusions: In patients with HCM despite recent iv bisphosphonate treatment, denosumab lowered serum calcium in64{\%}of patients within 10 days, inducing durable responses.Denosumabmay offer a new treatment option for HCM.",
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AU - Glezerman, Ilya G.

AU - Leboulleux, Sophie

AU - Insogna, Karl

AU - Gucalp, Rasim A.

AU - Misiorowski, Waldemar

AU - Yu, Bennett

AU - Zorsky, Paul

AU - Tosi, Diego

AU - Bessudo, Alberto

AU - Jaccard, Arnaud

AU - Tonini, Giuseppe

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AU - Braun, Ada

AU - Jain, Rajul K.

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N2 - Context: Hypercalcemia of malignancy (HCM) in patients with advanced cancer is often caused by excessive osteoclast-mediated bone resorption. Patients may not respond to or may relapse after iv bisphosphonate therapy. CopyrightObjective: We investigated whether denosumab, a potent inhibitor of osteoclast-mediated bone resorption, reduces serum calcium in patients with bisphosphonate-refractory HCM. Design, Setting, and Participants: In this single-arm international study, participants had serum calcium levels corrected for albumin (CSC) >12.5 mg/dL (3.1 mmol/L) despite bisphosphonates given >7 and ≤30 days before screening.Intervention: Patients received 120 mg sc denosumab on days 1, 8, 15, and 29 and then every 4 weeks.Main Outcome Measures: The primary endpoint was the proportion of patients with CSC ≤11.5 mg/dL (2.9 mmol/L) (response) by day 10. Secondary endpoints included response by visit, duration of response, and the proportion of patients with a complete response (CSC ≤10.8 mg/dL [2.7 mmol/L]) by day 10 and during the study.Results: Patients (N = 33) had solid tumors or hematologic malignancies. By day 10, 21 patients (64%) reachedCSC≤11.5 mg/dL,and12 patients (33%) reachedCSC≤10.8 mg/dL. During the study, 23 patients (70%) reached CSC ≤11.5 mg/dL, and 21 patients (64%) reached CSC ≤10.8 mg/dL. Estimated median response duration was 104 days. The most common serious adverse events were hypercalcemia worsening (5 patients, 15%) and dyspnea (3 patients, 9%).Conclusions: In patients with HCM despite recent iv bisphosphonate treatment, denosumab lowered serum calcium in64%of patients within 10 days, inducing durable responses.Denosumabmay offer a new treatment option for HCM.

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