Association of immune-related adverse events with survival and treatment outcomes in thymic tumors treated with immune checkpoint inhibitors.

Abstract

8111 Background: Thymic tumors are rare cancers with limited therapeutic options, particularly in refractory cases. Immune checkpoint inhibitors (ICIs) such as anti-PD1 and anti-PD-L1 antibodies have transformed cancer treatment, but data in thymic tumors remain scarce. We investigated the safety, efficacy, and biomarkers of ICIs in thymic tumors, focusing on immune-related adverse events (irAEs) and clinical outcomes. Methods: This study included patients (pts) with thymic tumors treated with ICIs at the University of Texas MD Anderson Cancer Center. The primary objective was to assess the occurrence, type, and severity of irAEs. Secondary objectives included evaluating clinical response using RECIST 1.1 and analyzing overall survival (OS) and progression-free survival (PFS) through Kaplan-Meier analysis. Cox regression was used to identify predictors of OS. Results: Forty-two pts (median age 58.5 years, 55% male) were analyzed: 29 (69%) had thymic carcinoma, 8 (19%) thymoma, and 5 (12%) thymic malignancy with neuroendocrine features. Pts had a median of one prior line of therapy (range 1-6) and received ICIs as monotherapy (n=23, 55%) or in combination with chemotherapy (n=9, 21%), other immunotherapies (n=6, 14%), targeted therapies (n=2, 5%), or other agents (n=2, 5%). irAEs occurred in 60% of pts (100% of pts with thymoma), with 9 pts (21%) experiencing severe irAEs (≥G3). Median time to develop ≥G3 irAEs was 42 days. Common all-grade irAEs included fatigue (19%), musculoskeletal toxicities (17%), and rash (17%), while the most frequent ≥G3 irAEs were musculoskeletal, myasthenia gravis (MG)-like, myocarditis, and hepatobiliary toxicities. Among the three pts with thymoma who developed MG-like symptoms, only one pt had a pre-existing diagnosis of MG. Two thymoma patients developed concurrent myocarditis and MG. One treatment-related death occurred due to pneumonitis in a patient with thymoma. Clinical benefit was observed in 69% of pts, including 9 partial responses (PR) (21%) and 10 with stable disease. Most pts (84%) with any-grade irAEs had SD or PR as best response with ICI. Median PFS was 195 days, with a 1-year PFS rate of 45%, while median OS was 274 days, with a 1-year OS rate of 44%. Pts with any-grade irAEs had improved OS (HR 0.3, 95% CI 0.11 -0.98, p = 0.04). Other OS predictors included TP53 mutations (HR 7.8, 95% CI 2.2 – 27.8, p = 0.002), CDKN2A alterations (HR 0.2, 95% CI 0.04-0.54, p = 0.004), African-American race (HR 10.9, 95% CI 3.7-32.3, p < 0.001), and lung metastases (HR 6.9, 95% CI 2.4 -19.8, p < 0.001). Conclusions: ICIs demonstrate promising efficacy in thymic malignancies, with higher toxicity rates in thymoma pts. The incidence of irAEs may serve as a prognostic marker for survival and treatment outcomes. Factors such as TP53, CDKN2A alterations, and lung metastases could guide patient selection for future ICI trials in thymic tumors.