Abstract PR007: Is sex an effect modifier for cancer immune checkpoint inhibitors? – A population-based study
Authors: Jang Se Ryeong , Nikita Nikita , Banks Joshua , Gandhi Krupa , Johnson Jennifer M. , Wilson Melissa , Keith Scott W. , Lu-Yao Grace 
Published: February 2021

Abstract
Background: Immune checkpoint inhibitors (ICIs) have revolutionized melanoma management and are now standard of care. While sex is associated with immune function and immune-related diseases, the interplay between sex and ICIs is under-studied. Therefore, we examined whether cancer immunotherapy effectiveness varied between female and male patients with advanced melanoma who are on either ipilimumab plus nivolumab combination therapy or anti-PD1 therapy, namely nivolumab or pembrolizumab.
Methods: Adults (age: 65+) with a record of melanoma diagnosis from 1991-2015 in the SEER-Medicare linked database were considered for the study. Only Stage III or IV melanoma patients whose claims records showed ipilimumab plus nivolumab (ipi/nivo) combination therapy or anti-PD1 therapy (i.e., nivolumab or pembrolizumab) as their last type of ICI prescribed were included in the analyses. Survival was defined as time from the first date of combination therapy or anti-PD1 therapy administration to death or loss of follow-up. We employed a Cox proportional hazards model to examine effect modification of sex on ICI while adjusting for prior use of ipilimumab, age at ICI initiation, Charlson Comorbidity Index, cancer stage at the time of diagnosis, and autoimmune disease diagnosis.
Results: We identified 165 advanced melanoma patients on ipi/nivo combination therapy and 1,204 advanced melanoma patients on anti-PD1 therapy (426 on nivolumab and 778 on pembrolizumab). More than 70% of the patient cohort were male, and approximately 10% of the cohort were diagnosed with at least one autoimmune disease. Compared to the anti-PD1 therapy patients, there were more patients at age &lt;70 (25.83% vs. 44.85%) and with no comorbidities (68.11% vs. 85.45%) on combination therapy. While everyone on the combination therapy had a history of taking ipilimumab prior to starting the current therapy, 30% of the anti-PD1 therapy patients were on ipilimumab previously. Given the unequal distribution of ipilimumab history between the ICI groups, we further divided our patient samples into the following 3 sub-groups: anti-PD1 patients with history of ipilimumab, anti-PD1 patients without history of ipilimumab, and combination therapy patients with history of ipilimumab. The interaction term between this treatment group classification and sex was statistically significant (p=0.009). Mortality hazard for female combination therapy patients with history of ipilimumab was 2.06 times (95% Confidence Interval: 1.28-3.32) higher than their male counterparts, and the difference was statistically significant (p=0.003). No significant difference was observed in other sub-groups.
Conclusions: This retrospective observational study showed that the risk of mortality among patients treated with ipi/nivo combination therapy may depend on the sex of the patient. Further studies are warranted to validate the study results.
This abstract is also being presented as PO052.
Citation Format: Se Ryeong Jang, Nikita Nikita, Joshua Banks, Krupa Gandhi, Jennifer M. Johnson, Melissa Wilson, Scott W. Keith, Grace Lu-Yao. Is sex an effect modifier for cancer immune checkpoint inhibitors? – A population-based study [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Cancer Immunol Res 2021;9(2 Suppl):Abstract nr PR007.