Incidence, risk factors, and outcomes of venous and arterial thromboembolism in immune checkpoint inhibitor therapy

Abstract

The risk of venous and arterial thromboembolism (VTE/ATE) associated with immune checkpoint inhibitors is currently unclear, and clinical trials evaluating these agents in patients with cancer did not provide information. Our aim was to quantify risk of VTE/ATE in a cohort of patients treated with immune checkpoint inhibitors, explore clinical impact, and investigate potential clinical risk factors. Patients treated with an immune checkpoint inhibitor at the Medical University of Vienna from 2015-2018 were identified using the in-house pharmacy records (n=672; most frequent entities: 30.4% melanoma, 24.1% non-small-cell lung cancer; 86% stage-IV-disease). A retrospective chart-review was performed to screen for VTE and/or ATE. Cumulative incidences and between-group differences were analysed within a competing-risk framework. Multi-state modelling was applied to study the impact of VTE/ATE on mortality. Over a median follow-up of 8.5 months, 47 VTE and 9 ATE were observed. Cumulative incidences of VTE and ATE were 12.9% [95% confidence interval (CI): 8.2-18.5)] and 1.8% [95%CI: 0.7-3.6]. Occurrence of VTE was associated with increased mortality (transition hazard-ratio (THR): 3.09 [95%CI: 2.07-4.60]. History of VTE predicted VTE occurrence (subdistribution hazard ratio (SHR): 3.69 [2.00-6.81]) and distant metastasis was non-significantly associated with VTE risk (SHR: 1.71 [95%CI: 0.62-4.73]). No association of VTE with ECOG performance-status, Charlson-Comorbidity-Index or the Khorana-score was observed, and rates of VTE were comparable among subgroups of tumour types and checkpoint-inhibitory agents. In conclusion, patients with cancer under immune checkpoint inhibitor therapy are at high risk of thromboembolism, especially VTE. Furthermore, VTE occurrence was associated with increased risk of mortality.

Increased incidence of venous thromboembolism with cancer immunotherapy

“…Ando et al 26 expanded on this report, describing VTE and ATE in 8.2% of a retrospective ll cohort of 122 individuals treated with pembrolizumab or nivolumab. Gutierrez-Sainz et al 34 described VTE in 16 of a cohort of 229 people with primarily lung cancers and melanoma over a median follow-up period of 9.8 months, and Moik et al 35 described a cumulative incidence of VTE and ATE in 12.9% and 1.8% of a cohort of 662 individuals with a median follow-up of 8.5 months. In our substantially larger analysis, we observed a similar incidence of VTE when comparable follow-up periods are examined, although our studies demonstrate that the risk of VTE extends beyond the initial 6-12 months of therapy.…”

Venous thromboembolism incidence and risk assessment in lung cancer patients treated with immune checkpoint inhibitors

“…The cumulative 6‐month VTE rate of 5% was similar to that in our study. The study included 162 NSCLC patients but cancer‐specific 6‐month VTE incidence was not reported 32 . Another study, published as a conference abstract, reported VTE rates of 10% ( n = 16, median 7‐month follow‐up) among 156 ICI‐treated patients with heterogenous cancer types, 27 whereas Sussman et al demonstrated VTE rates of 12.7% (12‐month follow‐up) in 219 melanoma patients treated with ICI, most of which occurred with the ipilimumab/nivolumab combination 33 …”

Similarities and perspectives on the two C’s—Cancer and COVID‐19

“…43 The new kids on the block anticancer therapy, immune checkpoint inhibitors, also are associated with a substantial risk of venous and arterial thromboembolism (cumulative incidences of venous and arterial thromboses were 12.9% [95% CI: 8.2-18.5] and 1.8% [95% CI: 0.7-3.6]). 44 The multisystem thrombosis would once again point to systemic coagulation activation in both the C's with all three constituents of the Virchow's triad coming into play. In relation to cancer, endothelial damage is caused by the tumor itself, chemotherapeutic agents, surgical interventions, and radiotherapy procedures, and stasis can occur from compression of vessels and immobility following surgery and general weakness and hypercoagulability from cancer procoagulants.…”