PSAT190 Denosumab use for life-threatening hypercalcemia of malignancy in a toddler. A weight base dose
Authors: Castano Gabriel , Alarcon-Mantilla Guido , Bhar Saleh , Bansal Nidhi 
Published: November 2022

Abstract

Introduction
Denosumab, an inhibitor of receptor activator of nuclear factor kappa-B ligand, has emerged as an important novel therapy for osteoporosis, hypercalcemia of malignancy (HCM), and other skeletal disorders in adults. While off-label use has been reported in children with these conditions, pediatric data is limited. We report a case of a 35-month old patient who had received Denosumab for management of life-threatening HCM.

Case
2-year-old male previously healthy who presented with increase work of breathing, altered mental status, and changes in his voice in the setting of progressive neck swelling over 2-weeks. Initial workup revealed a large mediastinal mass and metabolic anomalies including hypercalcemia (21.6mg/dL), shortened QTc on ECG, and acute kidney injury (AKI) stage 1-2 (eGFR 71 ml/min/1.73m2). Flow cytometry confirmed diagnosis of T-Cell ALL. PTHrP was 8.6pmol/L with a PTH of 7.1Pg/ml and a 25OH vitamin D of 38.9Ng/ml with 1,25OH of 6pg/ml.
On admission, patient started maintenance IV fluids, dexamethasone, calcitonin, and denosumab 0.3mg/kg. His calcium normalized by day 2-3 of treatment and eventually started oral calcium supplementation (25mg/kg elemental) with calcitriol to prevent hypocalcemia. Calcium stabilized with the lowest level at 7.6mg/dL on day 7; did not require IV calcium correction during hospitalization and renal function normalized. Patient was discharged on 0.5 mcg of calcitriol daily and 125mg/kg/day of elemental calcium.

Discussion
HCM develops in less than 1% of pediatric patients with cancer. Most cases are due to systemic parathyroid hormone-related protein, followed by osteolytic metastases leading to inflammatory cytokines locally released and least common via ectopic production of 1,25 dihydroxy vitamin D. HCM is an oncologic emergency. In adults, Denosumab has been used for HCM as a second-line agent after failure to respond to bisphosphonates, or when they are contraindicated. Bisphosphonates have shown to worsen renal function, even in those with normal glomerular filtration. Denosumab has been overall very well tolerated by patients. Initial hypocalcemia that peaks between days 4–10, and rebound hypercalcemia are one of the more feared side effects. Despite Denosumab not been cleared by the kidney, in adult patients with AKI or CKD, they have a higher risk of developing rebound hypercalcemia after receiving the standard 120mg SQ dose; a weight base dose was proposed, 0.3mg/kg for those with renal impairment. The reported dose in pediatrics for HCM has been 120mg, but we decided to do a weight base dose as our patient had AKI at presentation, with increased risk for decompensation once chemotherapy was started. Our patient responded very well to Denosumab with improvement in hypercalcemia, without severe hypocalcemia requiring IV calcium supplementation. Incidentally, to the best of our knowledge, our patient is the youngest patient reported to have received Denosumab for management of HCM.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.