Background/Objectives: Expanding use of immune checkpoint blockade (ICB) has led to a rise in immune-related adverse events, including immune-related pneumonitis (IRP), a potentially fatal condition.Corticosteroids remain first-line therapy for IRP, but prolonged use may reduce ICB efficacy, cause toxicity, and fail in refractory cases.Hydroxychloroquine (HCQ) has shown steroid-sparing effects in immune-related arthritis, yet its role in IRP remains unclear.This study evaluated HCQ as an adjunct to corticosteroid-based IRP management in melanoma patients.Methods: This retrospective single-centre cohort study included adult patients with metastatic melanoma treated with ICB at the University Hospital Zurich from November 2014 to January J o u r n a l P r e -p r o o f 2025 who developed Common Terminology Criteria for Adverse Events (CTCAE) grade 2 IRP.Patients were stratified by HCQ exposure.The primary outcome was cumulative corticosteroid dose; secondary outcomes included steroid duration, average daily dose, ICB resumption, and adverse events.Results: Among 46 melanoma patients with CTCAE grade 2 IRP, 10 patients received HCQ and 36 did not.HCQ-treated patients had higher cumulative steroid doses (median 4514 mg vs. 1627 mg) and longer therapy duration (131 vs. 85 days), without statistical significance.Following HCQ initiation, average daily corticosteroid dose declined from 88.9 mg/d to 23.3 mg/d, similar to HCQ-unexposed patients (23.1 mg/d).Notably, two HCQ-treated patients achieved IRP resolution without corticosteroids or further immunomodulation. Conclusions:Adjunctive HCQ was well-tolerated, with only one patient experiencing mild side effects.Limitations (small sample size, indication bias, confounding) preclude definitive conclusions.A prospective, randomized study is warranted to define HCQ's therapeutic role alongside ICB therapy.
Eicher et al. (Wed,) studied this question.