Racial disparities in immune-related adverse events (irAE) of immune checkpoint inhibitors (ICPi) and association with survival based on clinical and biochemical responses.

Journal of Clinical Oncology(2020)

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7025 Background: ICPi cause various irAE with thyroid dysfunction as a commonly reported abnormality. There is increasing evidence showing positive association with development of irAE and survival. However, prior trials with ICPi had underrepresentation of minorities with <5% African Americans (AA). Methods: We retrospectively reviewed patients (pts) with stage IV solid malignancies treated with PD1/PDL1 blockers between 1/2013-12/2018 across MedStar Georgetown Cancer Institute facilities. Pts treated with CTLA-4 inhibitors were excluded. Progression free survival (PFS) and overall survival (OS) were primary endpoints and were calculated using Kaplan-Meier methods and Wilcoxon rank sum test for comparison. Results: 293 pts met eligibility criteria. 91 pts (31%) had any grade irAE; most common AE were endocrine (40.7%) specifically TSH elevation, dermatological (23.1%) and rheumatologic (18.7%). Proportion of irAE was significantly higher in Caucasians versus AA (60.4% vs 30.8%), in pts with low PDL1, lower LDH, older age, and those who had more treatment cycles with ICPi. Rate of progression was lower in pts with irAE (30.8% vs 46.0%, p-0.0140). Median PFS (5.8 vs 3.0 months (mo), p- 0.0204) and OS (17.1 vs 7.2 mo, p value- <0.0001) were higher with irAE. Statistically significant difference in OS (17.1 vs 8.6 mo, p- 0.0002) but not in PFS (5.8 vs 3.3 mo, p: 0.0545) was noted with endocrine irAE. No differences in survival were observed among other commonly reported irAE. Differences in survival among subgroups of pts with irAE are detailed in table. Conclusions: Development of irAE positively correlated with improved PFS and OS as reported in previous studies. To our knowledge, this is the first study observing differences in OS favoring endocrine AE and Caucasian race. These factors may be potential surrogate markers of prognosis pending replication of these results in large-scale studies. [Table: see text]
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关键词
immune-related checkpoint inhibitors,racial disparities,adverse events,icpi
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