1263 Characterizing steroid-refractory immunotherapy toxicities and effect of second-line immunosuppression on clinical outcomes
Year: 2023
Type: conference-abstract
Abstract: Background Immune-related adverse events (irAEs) are major factors limiting optimal application of immune checkpoint inhibitors (ICIs). Up to 30% of irAEs are steroid-refractory, necessitating addition of second-line immunosuppression (2 nd-line IS).1 Unfortunately, there is a paucity of clinical studies describing factors that may predict steroid-refractory irAEs or their characteristics. Furthermore, it is unclear whether patients requiring additional immunosuppression beyond steroids have similar clinical outcomes as those requiring only steroids for irAE control.Methods We performed a retrospective cohort study to elucidate clinical characteristics that may be associated with development of steroid-refractory irAEs and examine the effect of additional 2 nd-line IS use on clinical outcomes of patients receiving ICIs. An electronic database search was performed for patients who received anti-PD-(L)1 and/or anti-CTLA-4 therapies for stage III-IV immunogenic (skin, GU, lung, GI) malignancies from 2013–2020 at Duke-affiliated hospitals; of these patients, those who were hospitalized and received IV methylprednisolone for treatment of severe irAEs were included in the study.Results Overall, a total of 214 patients were included in the study, with 64 (30%) requiring 2 nd-line IS. The most common steroid-refractory irAEs were enterocolitis (51.6%), pneumonitis (12.5%), and hepatitis (9.38%). The most common 2nd-line IS treatments required were infliximab (72%), IVIG (19%), and mycophenolate (9%). There was no significant difference in gender or age at ICI start, but there was a significant difference in race composition between the two groups. Surprisingly, patients who required 2nd-line IS had lower ECOG PS at ICI initiation compared to patients who did not require 2nd-line IS (0.53 vs. 0.86, p = 0.0025) and also had a lower Charlson comorbidity index at ICI start (7.53 vs 8.75, p < 0.0001). Those requiring 2nd-line IS had similar numbers of total severe irAEs requiring hospitalization than those not requiring 2nd-line IS (1.14 vs 1.23, p = 0.25). Those requiring 2nd-line IS had significantly longer durations of hospitalization (13.34 days vs 6.69 days, p < 0.0001),were significantly less likely to have their ICI re-introduced after admission (p = 0.03), and had higher rates of irAE-related mortality (p = 0.049)than those who did not.Conclusions Need for 2 nd-line IS for irAE control may increase duration of hospitalization, lead to fewer ICI re-introductions, and increase irAE-specific mortality, highlighting the importance of recognition, prediction, and prevention of steroid-refractory irAEs. Higher ECOG PS and comorbidity burden may be associated with need for 2nd-line IS. Further studies on effect of 2nd-line IS on survival outcomes are ongoing.Reference Horvat TZ, Adel NG, Dang TO, et al. Immune-related adverse events, need for systemic immunosuppression, and effects on survival and time to treatment failure in patients with melanoma treated with ipilimumab at Memorial Sloan Kettering Cancer Center. J Clin Oncol. 2015;33(28):3193–3198. doi:10.1200/JCO.2015.60.8448Ethics Approval This study was approved under IRB Pro00110199. As this study was a retrospective chart review of hospital visits that have already occurred using pre-existing clinical data in the electronic medical record, a waiver of informed consent was obtained.
Authors: Michelle Ferreira, Jennifer Guo, Tyler Jones, Steven Wolf, Christy Arrowood, Donna Niedzwiecki, Brent A Hanks
Institution: Duke University
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4388080340