The majority and diversity of clinical manifestations in LCH are attributed to immunological dysfunction resulting from langerhans cell (LC) derived cytokine secretion both at the lesional and systemic level. In a recent study, Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) was found to be abundantly expressed in cells within diverse LCH lesions from adult patients, especially in inflammatory infiltrates, a finding in line with a previously reported high osteoprotegerin (OPG) and low RANKL levels in the serum of patients with or without bone involvement. RANKL expression was associated with concomitant p65 Nuclear Factor Kappa-B (NFκB) nuclear staining, the main downstream effector of RANKL signaling, suggesting that lesional cell activation may be triggered locally by RANKL. Combining the serum and the lesional results, it can be inferred that there is an ongoing process of countervailing OPG production against lesional RANKL, which could be one of the self defense mechanisms among LCH patients. Therefore, the use of denosumab seems a rational treatment option in LCH in order to support and enhance the defensive OPG action and hopefully control or even interrupt the lesional immunological process.~The primary study objective is to assess the therapeutic efficacy of denosumab 120 mg every 8 weeks (Q8W) sc in adult LCH patients.~Secondary Objectives:~To define an uniform treatment approach for LCH patients with mild symptoms and low risk disease.~To explore the efficacy of denosumab 120 mg Q8W sc in reducing disease reactivations after treatment completion.~To illustrate the safety profile of denosumab in LCH patients. The primary efficacy endpoint is defined as the percentage of patients with progression of disease at Month 8.
This study is aiming to evaluate the efficacy of denosumab among adult patients suffering from Langerhans Cell Histiocytosis (LCH).