Immune checkpoint inhibitors and potential risk of thromboembolic events: Analysis of the WHO global database of individual case safety reports

Eman A Alghamdi; Hadir Aljohani; Waad Alghamdi; Fawaz Alharbi

doi:10.1016/j.jsps.2022.06.010

Immune checkpoint inhibitors and potential risk of thromboembolic events: Analysis of the WHO global database of individual case safety reports

Saudi Pharm J. 2022 Aug;30(8):1193-1199. doi: 10.1016/j.jsps.2022.06.010. Epub 2022 Jun 21.

Authors

Eman A Alghamdi¹, Hadir Aljohani¹, Waad Alghamdi¹, Fawaz Alharbi¹

Affiliation

¹ Saudi Food and Drug Authority, Riyadh, Saudi Arabia.

Abstract

Introduction: Thromboembolic events with the use of immune checkpoint inhibitors (ICIs) in patients with cancer have been reported in few studies. However, the detailed profile of these cases remains mostly uncertain.

Method: A descriptive analysis of Thromboembolic events associated with ICIs retrieved from the VigiBase, between 1967 to November 2020. We extracted the data using the terms of 'pulmonary embolism' OR 'deep vein thrombosis' OR 'acute coronary syndrome' OR 'myocardial infarction' OR 'ischemic stroke' (preferred term (PT) (MedDRA).

Results: We included 161 cases from 26 countries in our descriptive analysis. Patients' ages were reported in 141 (87.6%) cases, with a median of 68 years (interquartile range 61-74), and 63.4% of the patients were male. Indications for ICIs were reported in 151 (93.8%) cases, as follows: lung cancer (n = 85, 52.8%), renal cell carcinoma (n = 24, 14.9%), melanoma (n = 20, 12.4%), urethral carcinoma (n = 12, 7.45%), breast cancer (n = 4, 2.48%), adenocarcinoma of the gastroesophageal junction (n = 3, 1.9%), gastric cancer (n = 2, 1.24%), and skin cancer (n = 1, 0.62%). Nivolumab was reported as a suspected drug in 76 cases (47%), pembrolizumab in 46 cases (28.5%), atezolizumab in 21 cases (13%), durvalumab in 14 cases (8.6%), and avelumab in four cases (2.4%).The time to onset of thromboembolic events was reported in 127 (78.8%) cases. Most of these patients (n = 109, 85.8%) reported thromboembolic events within the first six months. The causality assessment of included cases showed that 50.3% of reported thromboembolic events were possibly related to the suspected reported medication, 13.7% were probably related, 13% were unlikely to be related, and 23% were not assessable due to insufficient information.

Conclusion: This study demonstrates a possible association between the use of ICIs and thromboembolic events. Further epidemiological studies are needed to assess this association and to elucidate the underlying mechanism.

Keywords: ACS, Acute Coronary Syndrome’; ADRs, Adverse Drug Reactions; ATE, Arterial Thromboembolism; Acute coronary syndrome; Checkpoints inhibitors; DVT, Deep Vein Thrombosis’; Deep vein thrombosis; IC, Information Component; ICIs, Immune Checkpoint Inhibitors; ICSRs, Individual Case Safety Reports; IQR, Interquartile Range; LMWH, Low-Molecular-Weight Heparin; MI, Myocardial Infarction; MedDRA, Medical Dictionary For Regulatory Activities; PD-1, Programmed Cell Death-1; PD-L1, Programmed Cell Death Ligand 1; PE, Pulmonary Embolism’; PT, Preferred Term; Pulmonary embolism; RR, Risk Ratio; TTO, Time To Onset; UFH, Unfractionated Heparin; UMC, Uppsala Monitoring Centre; VTE, Venous Thromboembolism; VigiBase; WHO, World Health Organization; irAEs, Immune-Related Adverse Events.