Sex differences in immune-related adverse events requiring hospitalization among patients with checkpoint inhibitor-sensitive malignancies: A national analysis.

Abstract

11169 Background: Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs) with significant morbidity/mortality. Sex influences immunity, yet sex-specific irAE patterns and outcomes in hospitalized patients remain underexplored. We investigated sex differences in irAE hospitalizations and mortality in ICI-sensitive cancers. Methods: Retrospective cohort study using the National Inpatient Sample (2019-2022) identified adults with ICI-sensitive malignancies (lung, melanoma, renal cell carcinoma [RCC], bladder, hepatocellular carcinoma [HCC]) and high-specificity irAEs (colitis, pneumonitis, cardiac, hepatic, dermatologic, neurologic) at academic centers. Primary outcome was in-hospital mortality. Secondary outcome was irAE distribution by sex. Multivariable logistic regression adjusted for demographics, cancer type, comorbidities, irAE type, discharge weights for national estimates. Results: Among 203,990 weighted hospitalizations (62.8% male; mean age 68), women had lower mortality (13.7% vs 15.0%; aOR 0.91, 95% CI 0.88-0.93, p<0.0001), consistent across models. Women had higher odds of neurologic (aOR 1.76, 95% CI 1.68-1.85), dermatologic (1.24, 1.20-1.29), hepatic (1.08, 1.05-1.11), and pneumonitis (1.05, 1.01-1.08) irAEs; men had higher GI colitis (aOR 0.51 for women, 0.48-0.53) and cardiac (0.81, 0.79-0.83) risks. Within irAEs, women had lower mortality for neurologic (6.0% vs 10.0%), pneumonitis (11.5% vs 14.2%), colitis (4.7% vs 6.5%), and dermatologic (4.5% vs 6.2%). Female survival advantage persisted across cancers (e.g., lung aOR 0.91, 0.87-0.94; HCC 0.95, 0.91-1.00) and after excluding autoimmune disease (aOR 0.93, 0.91-0.96). Temporal analysis showed widening sex gap (2019 aOR 0.99 to 2022 0.86; year × sex interaction p=0.0002). Conclusions: Women experience distinct irAE patterns (more neurologic/dermatologic) but lower overall and subtype-specific mortality versus men, with differences amplifying over time. Sex-stratified irAE surveillance and personalized ICI strategies can be implemented to optimize outcomes. In-hospital mortality by sex in irAE hospitalizations. Characteristic / Subgroup N (weighted) Male In-Hospital Mortality (%) Female In-Hospital Mortality (%) Adjusted OR (Female vs Male) 95% CI p-value Overall (Fully adjusted model¹) 203990 15 13.6 0.93 0.91-0.96 <0.0001 Overall (Fully adjusted + irAE type²) 203990 15 13.6 0.91 0.88-0.93 <0.0001 Lung Cancer 93135 16.2 14.2 0.91 0.87-0.94 <0.0001 Melanoma 6725 11.2 9.6 0.72 0.60-0.87 0.0006 Bladder Cancer 16795 10.3 8.4 0.74 0.64-0.85 <0.0001 GI Colitis irAE 17610 6.5 4.7 0.65 0.56-0.74 <0.0001 Pneumonitis irAE 21075 14.2 11.5 0.76 0.70-0.83 <0.0001 Dermatologic irAE 15215 6.2 4.5 0.62 0.54-0.73 <0.0001 Neurologic irAE 8695 10 6 0.66 0.55-0.79 <0.0001