Impact of ethnicity and immune-related adverse events (IRAE) on outcomes for non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors.
Authors: Resnick Karen , Zang Peter , Larsen Travis , Ye Shirley , Choi April , Yu Xiao , Brady Kevin , Angell Trevor E , Thomas Jacob Stephen , Nieva Jorge J. , In Gino Kim 
Published: June 2022

e21115

Background: Immune checkpoint inhibitors (ICI) have become the standard systemic therapy for the treatment of non-small cell lung cancers (NSCLC). With increased ICI use, the presence of immune related adverse events (IRAE) has increased and become associated with improved outcomes. However, minority populations are often underrepresented in clinical trials and the impact of ethnic variance on outcomes on ICI is not well defined. Methods: A retrospective analysis was performed on all NSCLC patients treated with ICI from 2014-2020 at Norris Cancer Center, Keck Medical Center, and Los Angeles County hospital. Presence of IRAE were determined by primary Oncology notes and graded per CTCAE v 5.5. Patients were divided by ethnicity/race below. All statistical analysis was performed with R. Results: In total, 186 NSCLC patients were treated with ICIs. The mean age was 66.3 years old (range 35-89) and average BMI was 25.1. Among the 186 patients, 65 (34.9%) were Asian/Pacific Islander (API), 60 (32.2%) non-Hispanic white (NHW), 33 (17.7%) Hispanic/Latino (HIS), 18 (9.7%) Black/African American (AA), and 10 (5.4%) Other. The median PFS and OS for the entire cohort was 7.1 mo and 17.3 mo, respectively. The median PFS and OS for API, NHW, HIS, and AA, were 18.7 and 20.3 mo, 7.37 and 25.3 mo, 4.1 and 11.0 mo, and 7.2 and 24.4 mo, respectively. The Hispanic group had significantly worse PFS (p = 0.01) and OS (p = 0.002), compared to all other groups. The rate of IRAE by patients was (36.0%), among which 46 (68.7%) were CTCAE grades 1-2 and 21 (31.3%) were grade 3 and above. Sixteen (23.9%) of the IRAE patients received steroids. The organ systems most affected by IRAE were Endocrine (28.4%) followed by Dermatologic (19.4%) and GI (17.9%). Among HIS, 24.2% experienced IRAE, compared to 41.5% for API, 41.7% for NHW, and 22.2% for AA. There was no significant difference in presence of IRAE (p = 0.1624) or the use of steroids (p = 0.3844) by ethnicity. Among the entire cohort, the presence of IRAE was significantly associated with improved median PFS (21.9 mo v 5.06 mo, p = 3e^-04) and median OS (47.7 mo v 12.7 mo, p = 4e^-05) when compared to no IRAE. The degree of improvement in OS with IRAE differed by ethnic/racial group and this difference between groups was statistically significant (p = 6e^-04). Comparisons of median OS with IRAE v without by ethnic/racial group, including hazard ratios: HIS (13.8 mo v 10.8 mo, -0.412), API (59.8 v 15.8 mo, -0.769), AA (41.1 mo v 12.5 mo, -0.924), NHW (47.7 mo v 19.3 mo, -0.958). Conclusions: Our data supports growing evidence that ICI outcomes differ by ethnic/racial background. Specifically, worse outcomes have been noted in the Hispanic population. While all groups show improved clinical outcomes from ICI when experiencing IRAE, this benefit appears to be less among the Hispanic population.