(P 42) RANKL-INHIBITION FOR GIANT CELL LESIONS OF THE JAW: A RETROSPECTIVE COHORT ANALYSIS

Objective: Giant cell lesion of the jaw is a rare benign osteolytic tumor that can demonstrate locally aggressive behavior. Traditional surgical management may lead to considerable morbidity and/or a high rate of recurrence for aggressive lesions. An underlying excessive RANKL expression is held responsible for the osteolytic activity. Therefore, this study aims to retrospectively assess the short-term and long-term efficacy and safety of RANKL inhibition in a cohort of patients diagnosed with GCLJ and treated with a one-year denosumab protocol within a collaborative network in the Netherlands.

Methods: A retrospective cohort study was conducted, compromising skeletally mature patients diagnosed with a primary or recurrent GCLJ and treated with a one-year protocol of monthly subcutaneously administered 120 mg denosumab. Objective tumor response based on histology and imaging was used to calculate objective tumor response rate (ORR), progression-free survival (PFS), and time to progression (TTP). The type, severity, and frequency of adverse events were recorded and graded using the CTCAE criteria v 5.0 to assess safety.

Results: Twenty patients who were predominantly female (90%) were included. Fifty-five percent of lesions were located in the mandible; 65% had not been previously treated. ORR was 100% after 12 months of treatment. Median PFS was 50.4 months (95% CI 38.0 – 62.8) with a cumulative progression-free survival rate of 22.6% (95% CI 1.8 – 43.4) at 5 years follow-up. Median TTP was 38.4 months (95% CI 26.0 – 50.8). Treatment was well tolerated, and none of the patients had to interrupt therapy for toxicity.

Conclusion: High-dose denosumab is effective and safe in achieving a complete response in GCLJ within 12 months, but there is a significant risk of progression after treatment discontinuation. Therefore, using RANKL-inhibition according to the described protocol is only justified for cases where other treatments have failed, or disease may lead to disfiguring mutilating surgery.