ICI-Induced Bullous Pemphigoid Common in Geriatric Patients

Jordan T. Said, BA

A new investigation into bullous pemphigoid found that elderly patients who received immune checkpoint inhibitors (ICIs) for the treatment of skin cancer were at an increased risk for developing the skin condition.

However, investigators observed that patients who developed ICI-induced bullous pemphigoids experienced relatively improved tumor responses.

In recent years, ICIs have dramatically changed the way providers treat late-stage and metastic cancers. Despite this, ICI therapy has been associated with various heterogeneous immune-related adverse events that occur in the skin of approximately 30-50% of treated patients, including bullous pemphigoid manifestation.

As such, investigators led by Jordan T. Said, BA, Brigham and Women’s Hospital in Boston, performed a case-control study – which was featured in a larger, multi-institutional retrospective cohort study- to identify the risk factors associated with ICI-induced bullous pemphigoid.

Investigators utilized patient registries from the Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Massachusetts GeneralHospital to identify ICI-induced bullous pemphigoid cases from October 1, 2014 to December 31, 2020.

All patients from the Dana-Farber Cancer Institute in particular were identified as controls.

Sex, ICI agents, ICE molecular target, and cancer type were collected from the cancer registry following ICI initiation as preselected potential risk factors, and age was categorized as younger than 70 years or 70 years or older.

Meanwhile, risk factors such as sex, race and ethnicity, cancer stage, metastasis sites, idiopathic bullous pemphigoid comorbidities, pre-ICI vaccination, radiation history, body mass index, and derived neutrophil-to-lymphocyte ration were assessed in the propensity score-matched case-control analysis.

Investigators evaluated the diagnosis of bullous pemphigoid at any point following ICI treatment via direct immunofluorescence, indirect immunofluorescence, autoantibody serologies, or diagnostic consensus among study board-certified dermatologists.

The best overall responses to ICIs between cases and controls were compared by Fisher exact test were compared in the secondary analysis.

A total of5636 patients from all participating centers were included in the study, a majority of whom were male patients (71.4%) with a median age of 72.8 years. Among these patients, 35 developed bullous pemphigoid.

Investigators utilized a multivariate logistic regression model to assess 2955 patients with complete data who were 70 years or older.

Among these patients, having melanoma (OR, 3.21, 95% CI, 1.51-6.58) (P < .003), and having nonmelanoma skin cancer (OR, 8.32, 95% CI, 2.81-21.13) (P < .001) were significantly associated with the development of bullous pemphigoid.

A complete or partial response on initial restaging imaging was observed as a risk factor for BP development (OR, 3.37, 95% CI, 1.35-9.30) (P = .01) in the nested 1:2 case-control comparison of all 35 cases to 70 propensity score-matched controls.

"Future work identifying risk factors and implications for other dermatologic adverse event phenotypes would be important for dermatologists, oncologists, and patients alike," the team wrote.

The study, "Risk Factors for the Development of Bullous Pemphigoid in US Patients Receiving Immune Checkpoint Inhibitors," was published online JAMA Dermatology.