Prognostic impact and risk factors of cancer‐associated thrombosis events in stage‐IV cancer patients treated with immune checkpoint inhibitors

Abstract

Background Cancer‐associated thrombosis (CAT) is a major cause of mortality in cancer patients. Immune checkpoint inhibitors (ICIs) have been associated with multiple side effects including CAT. The aim of this study is to investigate risk factors and prognostic impact associated with CAT events during ICIs treatment. Methods This is a multi‐center retrospective study that included stage IV cancer patients treated with ICIs. Results We identified 552 cancer patients treated with ICIs. During follow‐up time, 58 (10.5%) patients developed 67 venous thromboembolism (VTE) events while on ICIs. Anticoagulation use at the time of ICIs treatment start was associated with significantly higher VTE incidence rate (IRR: 2.23). No significant difference in VTE IRR was observed depending on response to ICIs treatment, aspirin use, or Khorana VTE risk score. Melanoma as primary cancer, Khorana score, ECOG status, and anemia at baseline were able to predict mortality. Conclusions The incidence of CAT in stage‐IV cancer patients treated with ICIs was higher in our study compared to previous reports. Control group of patients who did not receive ICIs is needed for better identification of CAT risk factors. Khorana score was a good predictor of mortality but not CAT risk and needs to be further validated in a homogenous group of patients.

Thrombotic Complications Associated with Immune Checkpoint Inhibitors

“…The references in the relevant articles were also manually searched for related studies. Overall, 18 retrospective studies reporting incidences and/or outcomes of venous and/or arterial thrombosis in patients on ICIs [ 1 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ] and 4 additional relevant systematic reviews and meta-analyses [ 24 , 25 , 26 , 27 ] were identified and included in this review.…”

“…The Khorana score was derived in a patient population starting a new line of chemotherapy, and whether it can be applied to patients on ICIs is not fully understood. Most studies that investigated the Khorana score for its prediction performance in patients receiving ICIs have not found it to be predictive [ 11 , 16 , 17 , 18 , 20 ]. This indicates that patients on ICIs likely have different sets of risk factors compared to those on chemotherapy, and a specific risk assessment model in this population may be needed.…”

“…However, most studies were small and single-center, and therefore, not surprisingly, different sets of risk factors were identified from each study, including a history of thromboembolic disease, metastasis, poor performance status, lung cancer, or melanoma, and more ( Table 2 ). It is worth noting that many of these studies tended to perform multivariable analyses with many variables from datasets with a limited number of patients and associated outcome events, leading to potential model overfit that could make results questionable [ 10 , 12 , 15 , 16 , 18 ]. Future research is needed to derive and validate a specific risk assessment model in a larger patient population receiving ICIs, which can help risk prediction and tailor thromboprophylaxis, if needed, in this growing population.…”

Risk Factors, Incidence, and Prognosis of Thromboembolism in Cancer Patients Treated With Immune Checkpoint Inhibitors

“…The presence of a stage IV tumor is also one of the reasons for the increased risk of TE in cancer patients receiving ICI treatment. In a retrospective cohort study, patients with stage IV tumors had an increased risk of TE ( Kewan et al, 2021 ). Similar results have been reported in the literature indicating that stage IV and/or metastatic disease are closely related to VTE ( Moik et al, 2021 ; Roopkumar et al, 2021 ).…”

“…According to the score, patients are assigned into low-, medium-, and high-risk groups. However, almost all current relevant studies have found that KS is not efficient for identifying cancer patients suitable for VTE prevention ( Nichetti et al, 2019 ; Icht et al, 2021 ; Kewan et al, 2021 ; Moik et al, 2021 ). Only one study has shown that a KS ≥ 1 is significantly associated with VTE ( Sussman et al, 2021 ).…”