Anti-PD-1 monotherapy in patients with malignant mesothelioma: A retrospective single institution experience.

Abstract

e20564 Background: Malignant mesothelioma (MM) patients historically have poor outcomes, but immune checkpoint inhibitors have shown promising results in certain patients. We aimed to retrospectively assess efficacy and safety with use of anti-PD-1 monotherapy (aPD-1 Tx) in patients with MM at our institution from Dec 2015 to Dec 2020. Methods: We identified patients with MM treated with nivolumab or pembrolizumab. Clinical details including demographics, efficacy, and toxicity were collected. Efficacy was characterized based on overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). Survival curves were generated using the Kaplan-Meier method, and intergroup comparisons were performed with the log-rank test. Univariable Cox regression analysis was used to determine whether variables were associated with survival. Results: We identified 61 patients treated with aPD-1 Tx for MM. Majority of patients (90%) had malignant pleural mesothelioma. Forty-two (69%) patients were male. The median age of initiation was 65 years (range: 30-84). Most patients (66%) had an ECOG performance status (PS) of 0-1. Known asbestos exposure was noted in 19 (31%) patients. Most patients had received prior chemotherapy (74%) and treated with nivolumab (89%). Only 66% of patients with known PD-L1 had positive expression ( > = 1%). There were 43 (70%) patients with epithelioid histology. Median follow-up was 22.2 months. ORR was 33% with stable disease in 25% of patients. In first-line aPD-1 Tx, ORR was 50%. PFS and OS at 12 months were 26% and 65%, respectively. The median PFS and OS were 5.1 and 15.6 months, respectively. PD-L1 positivity was not associated with improved PFS or OS. Univariable analysis demonstrated that ECOG PS 0-1 had significantly better OS with hazard ratio (HR) 0.40 (95% CI 0.20 – 0.83; p = 0.01). Immune-related adverse events (irAE) were seen in 33% of patients with 13 patients with grade 3 or higher (nephritis, pneumonitis, arthritis, leukocytosis, dermatitis, colitis, type 1 diabetes mellitus, tongue angioedema, and thrombocytopenia). One patient had grade 5 irAE due to severe thrombocytopenia. Patients who developed an irAE had significantly improved median OS (32.1 vs 12.1 months, p = 0.01). Conclusions: Anti-PD-1 monotherapy showed clinical efficacy and safety in malignant mesothelioma as both a first-line treatment and in pre-treated patients based on our real-world experience. The development of irAE may predict benefit, although fatal side effects can occur.