557 Antibiotic exposure for immune checkpoint inhibitor induced bullous pemphigoid associated with worse outcomes

Diversity of the gut microbiome is associated with improved response to immune checkpoint inhibitors (ICI). Microbiome diversity is greatly reduced with antibiotic use, and prior research demonstrates patients with advanced melanoma exposed to antibiotics prior to ICI initiation had statistically significant lower overall survival (OS) than unexposed patients. However, there are no published data investigating antibiotic use in patients experiencing ICI induced toxicities, despite dermatologic adverse events (dAE) occurring in approximately one quarter of these patients. ICI induced bullous pemphigoid (ICI-BP) is a well-established dAE where tetracycline antibiotics may be used. In this retrospective cohort study, we queried patient databases at a tertiary academic health system by ICD.10 codes and key-terms to retrospectively identify all ICI-BP patients, confirmed by three dermatologists. Patients were stratified to two groups, those with and those without antibiotic exposure for ICI-BP treatment, and OS was analyzed. Outcomes were adjusted in an inverse probability weighting regression, controlling for age, mucosal disease, vesicles or bullae, disease stage, chemotherapy before ICI, and number of prior cycles of ICI. There were 11 deaths in 35 ICI-BP patients (31%), with 44.4% (8 of 18) of the exposed group and 17.7% (3 of 17) of the unexposed group dying. Patients who took antibiotics had more than a 10-fold increase in the hazard of death compared with patients who did not take antibiotics (HR: 10.3, 95% CI: 1.7 to 63.8, p=0.01). Over half (55.6%) of the exposed patients had progressive BP despite antibiotics. As anti-inflammatory antibiotics may be used to treat dAEs, clinicians should be especially prudent with antibiotic use in ICI-BP patients, where utility appears limited. Further investigation of the impact of diverse antibiotic use among patients experiencing ICI induced dAEs is warranted.