Risk factors for cancer-associated thrombosis in patients undergoing treatment with immune checkpoint inhibitors

Invest New Drugs. 2020 Aug;38(4):1200-1206. doi: 10.1007/s10637-019-00881-6. Epub 2019 Dec 10.

Abstract

Purpose Anticancer agents are known to increase cancer-associated thrombosis (CAT) onset. CAT onset rate is reported to be 1.92% in cisplatin-based therapy, 6.1% in paclitaxel plus ramucirumab combination therapy, and 11.9% in bevacizumab monotherapy. Because immune checkpoint inhibitors (ICIs) cause a sudden increase in T cell number, an association between administration of these drugs and increase in CAT incidence is likely. However, the extent to which ICI administration affects CAT incidence remains unclear. Further, risk factors for CAT incidence have not yet been identified. The present study investigated CAT incidence and associated risk factors in patients receiving ICI. Methods Patients administered nivolumab or pembrolizumab at Fujita Health University Hospital from April 2017 to March 2018 were enrolled. We collected retrospective data regarding age, sex, cancer type, BMI, medical history, laboratory data at treatment initiation, medications, and computed tomography (CT) interpretations from electronic medical records. Results We identified 122 eligible participants from 135 patients receiving nivolumab or pembrolizumab. Ten patients (8.2%) developed CAT. A history of venous thromboembolism (VTE) or arterial thromboembolism (ATE) was a risk factor for CAT incidence (odds ratio: 6.36, P = 0.039). A history of heart disease may be a risk factor for CAT incidence (odds ratio 6.56, P = 0.052). Significantly higher usage of antiplatelet and anticoagulant therapy was noted in patients who developed CAT (60%) than in those who did not (13.4%, p < 0.01). Conclusion High (8.2%) CAT incidence during ICI administration suggested that ICI is not associated with a lower blood clot risk than other anticancer agents investigated in previous studies. For patients with VTE, ATE, or heart disease history, it is crucial to consider the possibility of CAT even with antiplatelet therapy.

Keywords: Arterial thromboembolism; Cancer-associated thrombosis; Immune checkpoint inhibitor; Nivolumab; Pembrolizumab; Venous thromboembolism.

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Anticoagulants / adverse effects
  • Antineoplastic Agents, Immunological / adverse effects*
  • Female
  • Heart Diseases / epidemiology
  • Humans
  • Immune Checkpoint Inhibitors / adverse effects*
  • Male
  • Middle Aged
  • Neoplasms / complications
  • Neoplasms / drug therapy*
  • Neoplasms / epidemiology
  • Nivolumab / adverse effects*
  • Platelet Aggregation Inhibitors / adverse effects
  • Retrospective Studies
  • Risk Factors
  • Thromboembolism / epidemiology
  • Thrombosis / epidemiology
  • Thrombosis / etiology*

Substances

  • Antibodies, Monoclonal, Humanized
  • Anticoagulants
  • Antineoplastic Agents, Immunological
  • Immune Checkpoint Inhibitors
  • Platelet Aggregation Inhibitors
  • Nivolumab
  • pembrolizumab