Background Multisystem immune-related adverse events (MsirAEs) are defined by the Society for Immunotherapy of Cancer (SITC) as irAEs occurring concomitantly with another irAE or during treatment for the first irAE. There is limited data describing overall incidence and patterns of MsirAEs across different tumor types. Immune checkpoint inhibitors (ICIs) have only recently been approved for treatment of breast cancer. We aimed to describe the patterns of MsirAE occurrence in this population.

Methods Multisystem immune-related adverse events (MsirAEs) are defined by the Society for Immunotherapy of Cancer (SITC) as irAEs occurring concomitantly with another irAE or during treatment for the first irAE. There is limited data describing overall incidence and patterns of MsirAEs across different tumor types. Immune checkpoint inhibitors (ICIs) have only recently been approved for treatment of breast cancer. We aimed to describe the patterns of MsirAE occurrence in this population.

Results We identified 108 patients who developed at least one irAE during the study period. Among these, 28% (n=30) had an MsirAE(characteristic details in table 1). Of those who developed an MsirAE, 90% had 2-system involvement of toxicities and 10% had 3-system involvement. The most common irAE identified as part of an MsirAEs cluster was hepatitis followed by hypothyroidism (table 2). There was no clear pattern of irAE co-occurrence or clustering as part of an MsirAE observed (table 3). The mean age of patients who developed an MsIrAE was 54y. Mean Charleson comorbidity score was 3.79. 70% of patients had an ECOG 0 at the start of ICI. 53% of patients had Stage III disease followed by 36% with Stage II .27% of patients who developed MsirAE had radiation treatment prior to ICI, and 50% had prior chemotherapy. Most common ICI used was Pembrolizumab (87%). ICI was given in the Neoadjuvant setting in 60% of patients. The mean time to development of the first irAE in the MsirAE cluster was 4 months after initiating treatment. Steroids were the most common treatment used in managing irAEs. 80% of patients who developed MsirAE did not resume ICI (n=24). Of the 6 patients who were rechallenged with ICI after MsirAE, 33% had irAE recurrence.

Conclusions Multisystem IrAEs were not uncommon among breast cancer patients treated with ICIs. We did not recognize a pattern of particular irAEs co-occurring as part of an MsIrAE cluster. Future directions are to identify potential risk factors for development of MsirAE among patients with breast cancer treated with checkpoint inhibitors.