Case Report: Successful treatment of steroid-refractory severe immunotherapy-induced pneumonitis with equine antithymocyte globulin

Abstract

Immune checkpoint inhibitors (ICI) have revolutionized melanoma treatment but are associated with autoimmune toxicities. Immunotherapy-induced pneumonitis (IIP) is a potentially fatal immune-related adverse event. Current management of IIP involves corticosteroids, mycophenolate mofetil (MMF), intravenous immunoglobulin, or infliximab for severe cases. Limited data exist for corticosteroid-refractory pneumonitis. This case report is the first to describe successful treatment of refractory grade 4 IIP with equine antithymocyte globulin (eATG) after failure of corticosteroids and MMF. A 50-year-old woman with recurrent unresectable melanoma in the right ankle developed grade 4 IIP after receiving two cycles of ipilimumab and nivolumab. Despite intravenous high-dose corticosteroid and MMF, her clinical condition continued to rapidly deteriorate. eATG was administered due to its rapid onset of T lymphocyte depletion and its use in immunotherapy-induced myocarditis. An 8-day course was delivered with dose adjustment to achieve therapeutic CD2+/CD3+ lymphocyte depletion. Clinical and radiological improvement was demonstrated, with successful weaning of oxygen and corticosteroids. At 12 months, the patient remained well from a respiratory standpoint, with no recurrence of melanoma. This case highlights the potential for eATG, with therapeutic CD2+/CD3+ T lymphocyte count monitoring, to address an unmet therapeutic need in patients with refractory ICI-induced IIP.