Effects of immune related adverse events and corticosteroids on the outcome of patients treated with immune checkpoint inhibitors

免疫相关不良事件和皮质类固醇对接受免疫检查点抑制剂治疗的患者预后的影响

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Abstract

Immune related adverse events (irAEs) occur due to the inflammatory side effects of immune check point inhibitors (ICIs) and irAEs have been associated with improved efficacy in advanced non-small lung cancer (NSCLC) patients. Corticosteroids can reduce the efficacy of ICIs due to their immunosuppressive effects. In this study, we aimed to show the effects of the development of irAEs and the use of ≥ 10 mg prednisone and equivalent steroids on treatment response. We analyzed the outcomes of patients with NSCLC treated with ICIs as monotherapy or ICIs in combination with chemotherapy (ChT) at a single academic center based on the presence of irAEs and the use of corticosteroids. A landmark analysis was performed due to the time-dependent nature of irAEs. 90 patients were included in the study. irAEs were seen in a total of 45 (50%) patients. In the landmark analysis, the median overall survival (OS) was 52.1 months in those who developed irAEs and 14.4 months in those who did not (HR 2.71, 95% CI (1.55-4.73), p < 0.001), and the median progression-free survival (PFS) was also higher in the patients with irAEs (25.9 vs. 8.4 months, HR 2.54, 95% CI (1.52-4.25), p < 0.001). The objective response rate (ORR) was significantly higher in patients experiencing irAEs than without irAEs: 60% versus 33.3%, respectively (p = 0.011). The number of patients using steroids was 22 (24%), while 68 patients (76%) were not using steroids. There was no significant difference in mOS: 26.5 versus 28.7 months (HR 1.14, 95% CI (0.63-2.08), p = 0.652) and mPFS: 16.9 versus 13.5 months (HR 0.99, 95% CI (0.57-1.74), p = 0.997) between patients who used steroids and those who did not. ICIs efficacy is higher in patients who developed irAEs. In our analyses, the grade of irAEs or the number of irAEs occurring in the individual had no effect on mOS and mPFS. In our patient group, steroid use was mostly related with irAEs, and we did not detect any negative effects of corticosteroid use on PFS and OS.

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