Success And Failure Of Additional Immunosuppressants In Steroid-Refractory Pneumonitis Related To Immune Checkpoint Blockade.

3078 Background: Severe immune related adverse events (irAEs) with immune checkpoint blockade are uncommon but can be fatal. Steroids are the most common initial treatment for most non-endocrine irAEs, but some patients are or become refractory to steroids. When steroids are not effective, there is limited data to guide management strategies, particularly in the context of pneumonitis. Methods: All patients at MSK treated with immune checkpoint blockade from 2013-2020 were queried for receipt of an immunosuppressant (e.g. TNF antagonists, mycophenolate mofetil, cyclophosphamide) beyond steroids. Patient records were then manually reviewed to identify patients who received such therapy for management of immunotherapy-related pneumonitis. Results: Among 5363 patients treated with immune checkpoint blockade, 364 (6.8%) received an additional immunosuppressant for an irAE, including 28 (0.5% of all patients treated) patients treated for pneumonitis. Most of these pneumonitis events (19/28, 68%) were grade 3 or higher. Agents used included mycophenolate mofetil (7/28; 25%), TNF antagonists (23/28; 82%), and cyclophosphamide (1/28; 3.5%); more than one medication was used in 3 patients (11%). The indications were primary non-response to steroids (n = 16, 57%) and recrudescence after initial response to steroids (n = 12, 43%). At 90 days from initiation of the additional immunosuppressant, 13/28 (46%) patients were alive with improvement or resolution of pneumonitis while 15/28 (54%) had died. Survival with resolution/improvement was more common in patients treated for recrudescence vs primary non-response (67% vs 25%, p = 0.05). Conclusions: Outcomes with additional immunosuppressants in the setting of steroid-refractory immune-related pneumonitis are poor, but resolution can occur in some cases. A deeper understanding of the mechanistic underpinnings of irAEs is needed to more effectively tailor immunosuppressant therapies, particularly in severe pneumonitis events.