Immune checkpoint inhibitors (ICI) in thymic epithelial tumors (TET): A real world assessment of efficacy and toxicity.

Abstract

e20141 Background: TET are rare and challenging entities in clinical practice. Prospective trials in thymoma and thymic carcinoma (TC) are scarce. Limited number of small trials investigated the role of ICI in TET, and showed some clinical efficacy, but also with immune related adverse events (irAE). Guidelines list ICI as a treatment option in the 2 nd line, although no FDA approval was granted. Aside from the small trials, there is limited real world data about the efficacy and toxicity of ICI in TET. Methods: We performed a retrospective chart review of the medical records of all patients (pts) with TET who were treated with ICI between 3/25/2011 and 11/30/2024 at 5 Mayo Clinic sites. We collected data about baseline characteristics, diagnosis, irAE, and outcomes. Kaplan-Meier method was used to calculate median progression free survival (mPFS), and hazard ratio (HR) with Cox proportional hazards regression. Results: 30 pts were included, 28 diagnosed with TC, and 2 with malignant thymoma. 70% of pts were male. Median age at time of diagnosis was 61 years (range: 15 to 82), and median ECOG at the time of diagnosis was 0. 29 pts received Pembrolizumab, and one received Durvalumab. Prior to ICI, 86.67% of patients received chemotherapy. 70% of pts discontinued ICI use, 60% due to progression, and 10% due to irAE. Overall response rate (ORR) was 23.33%, with 3.33% complete response, and 20% partial response. Disease control rate (DCR) was 63.33%. The mPFS was 10.13 months. At the time of analysis 60% of pts were still alive. 40% of patients had irAE. While the two patients with thymoma experienced irAE, only 33.33% of those with TC had these events. 26.67% of pts had thyroiditis. Pancreatitis, pneumonitis, dermatitis, and encephalitis each occurred in 3.33% of pts. The median time to irAE onset was 75 days. 25% of irAE were grade 1, 66.67% grade 2, 0% grade 3, and 8.33% grade 4, represented by the case of encephalitis. Resolution of irAE occurred in 33.33% of cases. When stratified according to the occurrence of irAE, the mPFS was the same in both groups, with or without irAE, being 10.13 months, HR=0.99 (95% CI 0.39 – 2.54). Conclusions: In this real-world cohort of pts with TET, efficacy of ICI matched what has been previously reported, with similar ORR and DCR, but with longer mPFS. However, irAE incidence was higher, but with less grade 3/4 events. Differently than what has been suggested in other diseases, irAE occurrence did not correlate with better outcomes. These results validate the role of ICI in the treatment of TET, especially TC. Nonetheless, improving patient selection, and developing other therapeutic strategies, including combinations of ICI and other drugs, for these malignancies remain essential. Importantly, the high incidence of irAE indicates that future investigations must also focus on safety of interventions and supportive care in TET.