Risk factors of developing multisystem immunotherapy-related adverse events among patients with breast cancer treated with immune checkpoint inhibitors.

Abstract

e14666 Background: Multisystem immune-related adverse events (MsirAEs) are defined as irAEs occurring concomitantly with another irAE or during treatment for the first irAE. There is limited data describing predictive risk factors for MSirAEs across different tumor types. Immune checkpoint inhibitors (ICIs) have only recently been approved for treatment of breast cancer. We aimed to describe the risk factors of MsirAE occurrence in this population. Methods: We conducted a case control study among female patients with breast cancer who were treated with an ICI between January 2017 and December 2022 at our comprehensive cancer center. Cases were defined as those who developed irAEs that met the criteria for a MsirAE. Patients in the control group did not develop any irAE. Descriptive statistics were used to summarize patient characteristics. We used univariate analysis to determine associations of candidate variables with having a MsirAE. Logistic regression was used to determine the effect of candidate covariates including demographic, clinical and treatment related variables, on the outcome. A stepwise selection was then performed using 0.05 for the significance level of the Wald chi-square for an effect to stay in the model. Results: We included 373 patients in our cohort. There were 49 cases of MsirAE (13%) and 324 controls Among patients with a MsirAE, the mean age was 50 years. Majority of cases had an ECOG of 0 (83%). Most cases had stage 3 disease at start of ICI (44%), followed by stage 4(31%), then stage 2(23%). Mean Charlson comorbidity index for patients who had MsirAE was 5. Most of patients were treated with pembrolizumab (76%) and patients received a mean of 9 cycles of immunotherapy. On univariate analysis only treatment with pembrolizumab showed an association with development of MsirAE (p=.04). Age, race, ethnicity, ecog, obesity history, charlson score, stage of disease, and number of cycles of immunotherapy received were not associated with developing a MsirAE. On regression analysis, treatment with Pembrolizumab seemed to have higher odds of developing MsirAE compared those not treated with Pembrolizumab (OR 2.059, CI 1.015, 4.179, p = 0.045). Conclusions: Multisystem IrAEs were not uncommon in our population with a prevalence of 13%. Pembrolizumab is one of 2 immunotherapy drugs approved by the FDA for breast cancer and is most utilized. In our analysis, treatment with pembrolizumab was found to be associated with development of MsirAE. It should be noted that patients who were on clinical trials for other immunotherapy agents were also included in our cohort. Our findings are not conclusive and further investigation of other potential risk factors for MsirAE should be studied. Future studies should explore if the development of a single irAE vs MsirAE is associated with tumor response to treatment and overall patient survival.