Background Previous studies have shown that combining immune checkpoint inhibitors (ICIs) with Talimogene Laherparepvec (TVEC) may improve antitumor responses for metastatic melanoma.¹ However, the risk of developing cutaneous immune-related adverse events (cirAEs) in patients treated with ICI and TVEC has not been studied. We aim to evaluate the differences in cirAE development between patients treated with ICI with or without TVEC.

Methods In this multi-institutional retrospective cohort study, patients with cutaneous malignancy receiving ICI with or without TVEC therapy at the Massachusetts General Brigham healthcare system between September 12, 2014, and May 31, 2022 were included. CirAE development, time from ICI initiation to cirAE, cirAE grade, cirAE morphology, and survival were analyzed. Manual chart review was conducted by two independent trained research analysts to determine cirAE development based on timing, morphology, competing risk factors, and histologic confirmation. To compare the cohorts, Pearson’s chi-squared test or Fisher’s exact test for categorical variables and t-test or Kruskal-Wallis test for continuous variables were used. To account for immortal time bias, we performed time-varying Cox proportional hazards models, adjusting for sex, race/ethnicity, age at ICI initiation, ICI type, Charlson Comorbidity Index, and cancer type. Hazard ratios (HRs) and 95% confidence intervals were calculated for all variables.

Results A total of 892 cutaneous malignancy patients treated with ICI and/or TVEC therapy were included in this study, among which 93 patients were treated with both ICI and TVEC (ICI+TVEC). While 799 patients were treated with ICI alone. The rate of cirAE development was 33.2% and 38.7% for ICI only and ICI+TVEC, respectively (table 1). After adjusting for covariates, ICI+TVEC was associated with a 2-fold increased risk of cirAE development (HR: 1.96, p=0.009), when compared to patients receiving ICI therapy alone (table 2).

Conclusions These findings underscore the elevated risk of cirAE in those receiving ICI+TVEC and highlight potential opportunities for dermatologists and oncologists in counseling and monitoring patients who are considering or receiving ICI and TVEC. More individualized education and management can improve decision-making and quality of life for patients and caregivers. Limitations of this study include its retrospective nature and limited sample size from a tertiary-level academic healthcare system.

Reference

1. Collins JM, Redman JM, Gulley JL. Combining vaccines and immune checkpoint inhibitors to prime, expand, and facilitate effective tumor immunotherapy. Expert Rev Vaccines. 2018;17:697–705.

Ethics Approval Reviewed and approved by Mass General Brigham Institutional Review Boards; protocol # 2020P002307