INNV-42. INTRA-ARTERIAL MELPHALAN FOR HISTIOCYTIC NEOPLASMS INVOLVING NEUROLOGIC, OCULAR, AND HEAD AND NECK STRUCTURES

Histiocytic neoplasms are clonal hematopoietic disorders of myeloid lineage. Involvement of neurologic structures by histiocytic infiltration or disease-associated neurodegeneration (ND) represents a severe disease phenotype associated with morbidity and mortality. Despite recent advances with BRAF and MEK inhibitors, patients with neurohistiocytic involvement continue to demonstrate suboptimal outcomes. Intra-arterial chemotherapy (IAC) may represent an effective therapy for this disease manifestation.

Patients with biopsy-proven histiocytic neoplasms involving neurologic, ocular, or head and neck structures were treated with intra-arterial melphalan delivered via selective catheterization of tumor arterial vasculature. Patients treated had refractory/persistent tumorous disease or progressive functional decline despite BRAF/MEK inhibition, or had limited disease appropriate for local therapy. Patients were evaluated for radiologic (PET or CT/MRI) response and functional neurologic response with quantified ataxia and dysarthria scales, or change in visual acuity (VA), as appropriate. Procedure-related adverse events as well as clinical and laboratory toxicities were captured.

74 IAC treatments were administered to 17 patients, 12 with tumorous disease (6 Rosai-Dorfman disease; 3 xanthogranuloma; 3 Langerhans cell histiocytosis[LCH]; 1 Erdheim-Chester disease [ECD]), 5 with ND-LCH/ECD, and ten with disease-related impairment of VA. Patients received a range of 2-12 IAC doses. 9/12 (75%) patients with tumorous disease had complete or partial radiologic response. 4/5 patients with ND had measurable improvement in dysarthria and 2/5 had measurable improvement in ataxia. 4/10 patients had improved VA. Of all patients with clinical or radiologic response, three have experienced disease recurrence since IAC in long-term follow-up. No procedural adverse events were observed, 1 patient had neutropenia and 1 patient melphalan hypersensitivity.

IA melphalan is a safe and robustly effective treatment option for tumorous and ND histiocytic neoplasms of neurologic, ocular, and head and neck structures.