Therapeutic Use of Recombinant Interferon-Gamma in Patients with Refractory Disseminated Coccidioidomycosis

• DOI: 10.70962/cis2025abstract.146
• Publication Date: 2025-04-25T20:14:36Z
• Authors: Chen Wang; Brenna LaBere; Michell Lozano Ch...; Keith Sacco; Wassim Ballan; James Woodward; Scott Ostdiek; Matthew Smith; Annalie Harris; Lindsey Rosen; Victoria Anderson; Janine Daub; Cindy Palmer; Fariba Donovan; John Galgiani; Alexandra Freeman; Christa Zerbe; Steven Holland
• Keywords: Refractory (planetary science)

Introduction Disseminated coccidioidomycosis (DCM) is a serious illness with significant morbidity and mortality, especially in patients impaired host defense mechanisms interferon-gamma (IFN-gamma)/interleukin-12 STAT3 axes. With standard treatments, these often require prolonged, sometimes lifelong, antifungal therapy, which are not curative. The therapeutic benefits of adjunctive IFN-gamma DCM remain unclear. Methods We conducted retrospective chart review treated at our institutions performed literature to identify additional cases. Treatment responses were assessed using modified EORTC/MSG criteria. Results identified 17 cases (12 from institutions, 5 the literature; 7 females) who received 19 courses therapy. Genetically confirmed inborn errors immunity included STAT1 gain function (GOF) 2 autosomal dominant partial IFNGR1 deficiency 1. median age first diagnosis was years (range: 4-57), interval initiation therapy 10 months 0.5-120). All had extensive diseases prior treatment, as evidenced by multiorgan involvement (median 4, including CNS involvement), despite various agents 4) surgical interventions 13 patients. Five required hospitalization intensive care unit, 1 on VV-ECMO. maximum dose 50 mcg/m2 (subcutaneous, range: 25-200 mcg/m2, 3×/week) treatment duration 8 2-39). Adverse events recorded They uncomfortable but manageable supportive all, except for three ultimately discontinued because cytopenia, headache, fever, respectively. Of courses, there 11 responses, 3 nonresponses, both GOF eventually died DCM. In those achieved least improvements observed C-reactive protein levels (pre- vs. post-treatment, 42.6 7.0 mg/L, p = 0.001), anti-Coccidioides antibody titers (1:128 1:16, 0.002). No neutralizing anti–IFN-gamma autoantibodies detected before, during, or after Conclusion failed may provide other treatments.