A41-28 When Steroids Are Not Enough: Second Line Options for Checkpoint Inhibitor-Related Pneumonitis

Abstract Introduction Immune-mediated checkpoint inhibitor (ICI) pneumonitis is a potentially fatal outcome of anti-PD-1 therapy. Patients who do not improve with cessation of therapy and corticosteroids are noted to have steroid-refractory pneumonitis, which is associated with high mortality risk 1. There are currently no standardized treatments for these patients, though emerging research highlights the use of second-line agents including cyclophosphamide, intravenous immunoglobulin (IVIG), infliximab, or mycophenolate. Here, we present a patient with steroid-refractory pneumonitis treated successfully with IVIG. Case A male, age mid-50s, with a history of COPD, tobacco use, and small cell lung carcinoma (SCLC) with metastasis to brain presented with 1 week of exertional dyspnea. For SCLC, he had chemotherapy with cisplatin/etoposide followed by 9 cycles of pembrolizumab, last dose 1 month prior to presentation. He was admitted to the ICU on high flow nasal cannula (HFNC). CT scan showed ground glass opacities, septal thickening, and interstitial consolidations bilaterally, concerning for infection versus ICI pneumonitis. He received 7 days of antibiotics, though sputum cultures grew only normal oral flora. He received methylprednisolone 2mg/kg/day for pneumonitis but continued to have hypoxia requiring HFNC. Given lack of adequate response to steroids, he was treated with IVIG 1000mg/kg daily on admission days 5 and 6. On admission day 9, his oxygen saturations improved. He started pulse-dose steroids (methylprednisolone 1000mg/day for 3 days) starting on admission day 10 with further improvement. He was discharged with a prednisone taper. Conclusion ICI pneumonitis remains a clinical diagnosis without pathognomonic radiographic findings. Patients are often treated concomitantly for ICI pneumonitis and pneumonia, as in this case. Our patient had steroid-refractory pneumonitis, with lack of response after 48-72 hours of steroid therapy. Second-line therapy with IVIG and pulse-dose steroids led to improvement in oxygenation. The use of these second-line therapies is understudied. Case reports have shown success with infliximab or IVIG 6, 8. Observational studies have shown improvement with IVIG, infliximab, cyclophosphamide, mycophenolate, or combinations thereof, though mortality is still high from pneumonitis and infection 1, 2, 3, 5. Overall, outcomes in ICI pneumonitis with IVIG treatment have been promising in the reviewed literature and in our patient’s case. The use of pulse-dose steroids is also worthy of further study, though current corticosteroid recommendations are 2mg/kg followed by a prolonged taper 4, 7. Overall, ICI pneumonitis is difficult to definitively diagnose, and outcomes are generally poor; so it is essential to explore potential second line management options. This abstract is funded by: None