Ipilimumab pneumonitis treated with Infliximab

INTRODUCTION: Immune checkpoint inhibitors, which aim to amplify the body's own defence mechanism by removing inhibitory pathways, were initially thought to eliminate the well-known toxicities associated with traditional cancer therapies. However, immune checkpoint protein inhibition has been associated with a unique spectrum of immune-related adverse events (IrAEs) that mimic a variety of autoimmune syndromes. Symptomatic pneumonitis is more common among patients treated with antiprogramed cell death-1 therapies but is also seen with anticytotoxic T-cell ligand-4 inhibitors and combination therapies. Case: We present a 66 year old male with metastatic pancreatic cancer who received two cycles of Evofosfamide and Ipilimumab. His had elevation of liver enzymes due to immune mediated hepatitis, so his therapy was held. He was treated with high dose oral steroids for several weeks. Once the steroids began to taper, he noticed worsening dyspnea with exertion as well as fever and cough. Symptoms progressed until he was unable to ambulate a few feet and he presented to the emergency center. Chest imaging showed new bilateral pulmonary opacities suspicious for immunotherapy related pneumonitis (a). He was admitted and started on empiric antibiotic and antifungal therapy and high dose IV steroids for possible infection and presumed pneumonitis. Diagnostic bronchoscopy was not feasible given his respiratory insufficiency and high-flow oxygen requirement. After one week of empiric therapy, infliximiab was administered with significant decrease in oxygen requirement and radiographic improvement within 48 hours. He was discharged with a prolonged steroid taper and repeat imaging 4 weeks later showed almost complete resolution (b). Discussion: Pneumonitis associated with immune checkpoint therapies is a rare but potentially fatal cause of lung-related IrAEs. It can develop at any time during a patient's treatment course and has diverse clinical, radiological and pathologic features. It may be the sole IrAE, or occur simulataneously or sequentially with other IrAEs. Treatment guidelines are based on observational reports and clinical experience, and these have not been standardized or validated in prospective clinical trials. The optimal immunosuppressive therapy choice, dose, and duration have not been studied but Infliximab has shown promise in reducing treatment time of immune-related enterocolitis and sparing toxicity of prolonged steroid exposure. Further studies to determine if this can be translated to apply to pneumonitis are needed.