Incidence of venous thromboembolism and discriminating capacity of Khorana score in lung cancer patients treated with immune checkpoint inhibitors

Abstract

Venous-thromboembolism (VTE) is increased in lung cancer patients (LCP) treated with immune-checkpoint inhibitors (ICIs) but risk factors are not identified and the Khorana Score (KS) is not validated. To assess VTE incidence and its clinical impact, to investigate potential clinical risk factors and KS performance in LCP. Retrospective analysis of LCP initiating ICIs treatment between June 2015 and November 2020 in a for-profit cancer center. 481 patients were included: 62% adenocarcinoma, 70% PDL1 + , 86% stage-IV-disease. Over a median follow-up of 9.8 months, 47 VTE were observed: 28 pulmonary embolisms, 15 deep venous thromboses (distal n = 9, proximal n = 6), 3 inferior vena cava thromboses, 1 other VTE, no superficial or digestive vein thrombosis. Median time from ICIs' initiation to VTE was 180 (11-1277) days. Overall survival was significantly lower in patients who experienced VTE (42.5 vs. 86.8 months, p = 0.006). In univariate analysis patients VTE was more frequent in metastatic patients (11.1% vs. 1.5%, p = 0.015) and lower in those treated with durvalumab (1.9% vs. 9.6%, p = 0.046). Logistic regression analysis showed that non-metastatic status (OR 0.13; 0.02-0.95, p = 0.04) and BMI (OR 1.07; 1.01-1.14, p = 0.028) were associated with VTE. The rate of VTE was the same in patients with a KS < or ≥ 2 (10.2% vs. 9.3%, p = 0.87). ICIs-treated LCP are at high risk of thromboembolism. VTE has a negative impact on survival. KS does not perform well in LCP. It is important to identify which VTE prediction models are available to be used in adult ambulatory lung cancer patients.

Keywords: Immune-checkpoint inhibitors; Khorana score; Lung cancer; Venous thromboembolism.