Immune checkpoint inhibitors-associated thrombosis in patients with lung cancer and melanoma: a study of the Spanish society of medical oncology (SEOM) thrombosis and cancer group

Abstract

Purpose Immune Checkpoint Inhibitors (ICI) can be associated with thrombotic events, both venous and arterial (VTE/AT). However, there is a paucity of information regarding patients in routine clinical practice. Methods/patients Retrospective, multicenter study promoted by the Thrombosis and Cancer Section of the Spanish Society of Medical Oncology (SEOM). Patients with melanoma and lung cancer who initiated ICI between 01/01/2015 and 31/12/2019 were recruited. Minimum follow-up was 6 months (unless it was not possible because of death). The primary objective was to calculate the incidence of ICI-associated VTE/AT and the secondary objectives included to analyze its impact on survival and to identify predictor variables for VTE/AT. Results 665 patients with lung cancer were enrolled. The incidence of VTE/AT during follow-up was 8.4%. Median overall survival (OS) was lower in the VTE/AT group (12 months 95% CI 4.84–19.16 vs. 19 months 95% CI 16.11–21.9; p = 0.0049). Neutrophil/lymphocyte ratio (NLR) and anemia upon initiation of IT, as well as a history of thrombosis between cancer diagnosis and the start of ICI, were predictive variables for developing of VTE/AT (p < 0.05). 291 patients with melanoma were enrolled. There was a 5.8% incidence rate of VTE/AT during follow-up. Median OS was lower in the VTE/AT group (10 months 95% CI 0.0–20.27 vs. 29 months 95% CI 19.58–36.42; p = 0.034). NLR and lactate dehydrogenase (LDH) at the beginning of ICI were predictor variables for VTE/AT (p < 0.05). Conclusions ICI increases the risk of VTE/AT in patients with lung cancer and melanoma, which impact OS.

Associations Between Immune-Related Venous Thromboembolism and Efficacy of Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

“…Of these, 7 studies evaluated exclusively VTE irAE, [28][29][30][31][35][36][37] and 6 studies evaluated mixed arterial and venous thrombotic complications in general but also provided details on VTE irAE. 27,[28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] Furthermore, 3 28,29,37 of the 7 studies that specifically assessed VTE irAE were positive, meaning they observed an excellent correlation between ICIs-related VTE and poor clinical outcomes, and 4 were negative. 30,31,35,36 As for studies that reported on both arterial and VTE/AE irAEs, all of the studies were positive, 27,[28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] meaning that they were significantly associated with a worse prognosis.…”

Immune Checkpoint Inhibitors-Associated Thrombosis: Incidence, Risk Factors and Management

“…However, risk factors found varied significantly among studies, as most studies were single-center with small sample sizes ( Table 4 ). Potential risk factors identified included (1) patient-related factors, such as female gender [ 20 , 28 ], history of thromboembolism [ 22 , 24 , 27 , 35 , 37 , 38 , 39 , 46 ], younger age [ 26 , 27 , 47 ], smoking [ 23 , 26 ], and poorer ECOG status [ 29 , 39 ]; (2) cancer-related factors, such as lung cancer [ 22 , 25 ], and metastasis [ 36 , 37 , 47 ]; and (3) treatment-related factors, such as combined ICI use [ 46 ], combined chemotherapy and ICI use, and more. A specific risk prediction model in this population to help identify patients at high risk who could benefit from primary thromboprophylaxis will be of interest.…”

“…In addition, worsening survival has been shown in patients with thrombosis (either VTE or combined venous and arterial thrombotic events) in this population in many studies [ 18 , 19 , 35 , 36 , 37 , 38 , 46 ], while some other (but fewer) studies did not show such an association [ 26 , 28 , 31 ]. The discrepancy could be due to factors such as patient population, type, and status of cancer.…”

Risk Factors of Venous Thromboembolic Disease in Cancer Patients Treated with Immune Checkpoint Inhibitor

“…[16][17][18][19][20][21][22][23] Although pathophysiological mechanisms, risk factors, and prognostic factors are beginning to be studied, including tumor stage and history of VTE, more data are needed to clarify the association between venous thrombosis and ICI. [24][25][26] The objective of this study was to analyze, in a real-life population, the risk factors of VTE in patients with cancer treated with ICI.…”

“…16 17 18 19 20 21 22 23 Although pathophysiological mechanisms, risk factors, and prognostic factors are beginning to be studied, including tumor stage and history of VTE, more data are needed to clarify the association between venous thrombosis and ICI. 24 25 26…”