Excellent Results in the Off-Label Use of Denosumab in Pediatric Oncology: Monocentric Case Series Study

Denosumab is a human monoclonal antibody approved by the Food and Drug Administration in 2013 for use in adults with inoperable giant cell tumor of bone (GCTB). In children, it is used as an off-label drug in some giant cell-rich tumors of bone (GCRTB) and giant cell granuloma (GCG). The aim of the study is to evaluate the efficacy and acute toxicity of denosumab in children. From February 2022 to December 2023, at the Istituto Giannina Gaslini, 5 patients were treated with denosumab, 2 females and 3 males. Age ranged from 8 to 17 years. Two had ABC (hemipelvis and D9), and 3 had GCG (sphenoid, jaw, and maxilla). An assay of calcium and vitamin D as well as a dental scan was performed before administering denosumab due to possible side effects such as hypocalcemia and jaw osteonecrosis. Therapy was given subcutaneously at the dose of 70 mg/m² (weight < 50 kg) or 120 mg (weight > 50 kg) at days +1, +8, +15, +28, and then monthly for 3-5 months, followed by imaging evaluation. Overall, 21 doses were administered to Patient 1, 20 doses to Patient 2, 11 doses to Patient 3, 10 doses to Patient 4, and 9 doses to Patient 5. Calcium carbonate and vitamin D were given as supportive therapy. We observed lesion volume reduction in 4 patients and radiological stability in 1 patient. Surgery was possible in 1 case thanks to the significant reduction of lesion size. A longer administration over 22 months was safe and well tolerated. No disease progression or side effects were observed. This study confirms literature data about the use of denosumab in inoperable GCRTB. These results are preliminary; further studies are necessary on a larger series of cases, with a longer follow-up (3-5 years), with data collection even from other pediatric centers.