9520 Background: The combination of ipilimumab (ipi), and nivolumab (nivo) has been shown to be a highly effective treatment for metastatic melanoma. However, immune-related adverse events (irAEs) are common with this treatment, leading to treatment interruption and the use of immunosuppressive agents. There are no data on the impact of resuming single agent nivo on survival outcomes following recovery from the irAE and completion of immunosuppressive treatment. Some physicians hold therapy permanently as done on clinical trials and other physicians resume nivo after steroid taper. Methods: In this retrospective analysis, we examined a cohort of patients treated with ipi/nivo who developed irAEs that required treatment interruption and immunosuppressive therapy. The differences in practice patterns among physicians at our institution allowed us to examine the effect of single agent nivo resumption on survival after treatment of irAEs. Multivariate analysis of clinical factors associated with improved survival was performed. Results: We identified 165 patients who were treated with ipi/nivo and developed irAEs requiring treatment interruption and immunosuppressive therapy. To remove any impact of immediate disease progression on the analysis patients who progressed on ipi/nivo prior to or during treatment hold were removed from analysis. Of the remaining 131 patients, 45 resumed single agent maintenance nivo following the resolution of toxicity and completion of steroid taper. When stratified by age and adjusted for sex, M-stage, LDH, duration of therapy, and type of irAE causing the treatment pause, the effect of resumption of nivo upon survival remained highly significant (p = 0.001). Patients who resumed nivo had an 82% reduction in the hazard of death compared with patients who had not yet or never resumed nivo (HR: 0.18, 95% CI: 0.06 to 0.52). Of the patients who resumed nivo, 12 (26%) patients had subsequent irAEs with 5 patients having grade 3 irAEs (only one of whom had a recurrence of the prior ipi/nivo associated toxicity) and no grade 4 or 5 irAEs were noted. Conclusions: The resumption of single agent maintenance nivolumab following a treatment hold for ipi/nivo associated irAE and completion of immunosuppressive therapy increased overall survival compared to discontinuing nivo permanently in patients with metastatic melanoma after stratification for many factors. Toxicity observed post resumption of single agent nivolumab was manageable with no severe irAEs observed. These results suggest that restarting maintenance nivo post irAEs should be studied prospectively.