Beyond Steroids: Immunosuppressants in Steroid-Refractory or Resistant Immune-Related Adverse Events

Introduction: The optimal management for immune-related adverse events (irAEs) in patients who do not respond or become intolerant to steroids is unclear. Guidelines suggest additional immunosuppressants on the basis of case reports and expert opinion. Methods: We evaluated patients with lung cancers at Memorial Sloan Kettering Cancer Center treated with immune checkpoint blockade from 2011 to 2020. Pharmacy records were queried to identify patients who received systemic steroids and an additional immunosuppressant (e.g., tumor necrosis factor-alpha inhibitor, mycophenolate mofetil). Patient records were manually reviewed to evaluate baseline characteristics, management, and outcomes. Results: Among 2750 patients with lung cancers treated with immune checkpoint blockade, 51 (2%) received both steroids and an additional immunosuppressant for a severe irAE (tumor necrosis factor-a inhibitor (73%), mycophenolate mofetil (20%)). The most common events were colitis (53%), pneumonitis (20%), hepatitis (12%), and neuromuscular (10%). At 90 days after the start of an additional immunosuppressant, 57% were improved from their irAE, 18% were unchanged, and 25% were deceased. Improvement was more common in hepatitis (five of six) and colitis (18 of 27) but less common in neuromuscular (one of five) and pneumonitis (3 of 10). Of the patients who died, 8 of 13 were attributable directly to the irAE and 4 of 13 were related to toxicity from immunosuppression (three infection-related deaths, one drug-induced liver injury leading to acute liver failure). Conclusions: Steroid-refractory or resistant irAEs events are rare. Although existing treatments help patients with hepatitis and colitis, many patients with other irAEs remain refractory or experience toxicities from immunosuppression. A more precise understanding of the pathophysiology of specific irAEs is needed to guide biologically-informed treatments for severe irAEs. (C) 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc.

Automated summary

The study evaluated the management and outcomes of immune-related adverse events in lung cancer patients treated with immune checkpoint blockade. Results showed that while steroid-refractory or resistant irAEs events are rare, many patients with other irAEs remain refractory or experience toxicities from immunosuppression. Further understanding of the pathophysiology of specific irAEs is needed to guide treatments for severe irAEs effectively.