A case of late and lethal Trousseau's syndrome induced by pembrolizumab in lung adenocarcinoma
Abstract
Trousseau's syndrome is a relatively rare reported event in immunotherapy-related clinical trials, mostly occurring in the early period of immune checkpoint inhibitor (ICI) therapy. Here, we report an unusual case of late and lethal Trousseau's syndrome during pembrolizumab maintenance therapy in a lung adenocarcinoma harboring tumor protein p53 (TP53) mutation. The patient has experienced severe coagulation abnormalities manifesting as cerebral infarction, partial infarction of both kidneys and spleen after 23 cycles of pembrolizumab use and was resistant to anticoagulants. The late occurrence of coagulation abnormalities in this case reveals a possible correlation between TP53 mutations and Trousseau's syndrome when patients are treated with ICIs.
Plain language summary
In clinical practice, symptoms associated with abnormal coagulation or fibrinolytic function in malignant tumors are known as Trousseau's syndrome. Its main clinical features include cerebral infarction, myocardial infarction, peripheral arterial embolism, etc. Trousseau's syndrome is a relatively rare reported event in immune checkpoint inhibitors (ICIs)-related clinical studies, mostly occurring in the early period of ICI therapy. Here, we report an unusual case of late and lethal Trousseau's syndrome during pembrolizumab, one of the ICI agents, maintenance therapy in a lung adenocarcinoma harboring tumor protein p53 (TP53) mutation. This patient has experienced severe coagulation abnormalities manifesting as cerebral infarction, partial infarction of both kidneys and spleen after 23 cycles of pembrolizumab use and was resistant to anticoagulants. The late occurrence of coagulation abnormalities in this case reveals a possible correlation between TP53 mutations and Trousseau's syndrome when patients are treated with ICIs.
Papers of special note have been highlighted as: • of interest; •• of considerable interest
Reference
- 1. Cancer statistics, 2021. CA Cancer J. Clin. 71(1), 7–33 (2021).
- 2. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N. Engl. J. Med. 375(19), 1823–1833 (2016).
- 3. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet 393(10183), 1819–1830 (2019).
- 4. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N. Engl. J. Med. 378(22), 2078–2092 (2018).
- 5. Trousseau's syndrome: cancer-associated thrombosis. Jpn. J. Clin. Oncol. 46(3), 204–208 (2016). • Overview of the clinical presentation, prevention and treatment for Trousseau's syndrome.
- 6. Oncogenic events regulate tissue factor expression in colorectal cancer cells: implications for tumor progression and angiogenesis. Blood 105(4), 1734–1741 (2005). •• Mechanism of TP53 mutation regulating tissue factor expression.
- 7. . Biological basis of personalized anticoagulation in cancer: oncogene and oncomir networks as putative regulators of coagulopathy. Thromb Res. 140(Suppl. 1), S37–S43 (2016).
- 8. Oncogenes, trousseau syndrome, and cancer-related changes in the coagulome of mice and humans. Cancer Res. 66(22), 10643–10646 (2006).
- 9. Clinical and molecular correlates of PD-L1 expression in patients with lung adenocarcinomas. Ann. Oncol. 31(5), 599–608 (2020).
- 10. Disorder of coagulation-fibrinolysis system: an emerging toxicity of anti-PD-1/PD-L1 monoclonal antibodies. J. Clin. Med. 8(6), 762 (2019). •• Relatively comprehensive summary of coagulation-fibrinolysis system adverse events associated with anti-PD1/PD-L1 antibodies.
- 11. Venous thrombotic events in patients treated with immune checkpoint inhibitors for non-small cell lung cancer: a retrospective multicentric cohort study. Thromb Res. 205, 29–39 (2021). •• The main clinical study of the relationship between coagulation and immune checkpoint inhibitors (ICIs) for non-small-cell lung cancer (NSCLC).
- 12. Trousseau's syndrome triggered by an immune checkpoint blockade in a non-small cell lung cancer patient. Eur. J. Immunol. 48(10), 1764–1767 (2018). • A case report for Trousseau's syndrome occurred in the early period of ICI initiation.
- 13. . Role of tissue factor in cancer. J. Clin. Oncol. 27(29), 4834–4838 (2009). • Relatively comprehensive summary of role for tissue factor in cancer.
- 14. . Trousseau's syndrome: multiple definitions and multiple mechanisms. Blood 110(6), 1723–1729 (2007).
- 15. Increased tissue factor expression is associated with reduced survival in non-small cell lung cancer and with mutations of TP53 and PTEN. Clin. Chem. 55(10), 1834–1842 (2009). •• The main clinical study of TP53 mutation regulating tissue factor expression in NSCLC.
- 16. Pembrolizumab-induced acute thrombosis: a case report. Medicine (Baltimore) 97(20), e10772 (2018).
- 17. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N. Engl. J. Med. 373(17), 1627–1639 (2015). • A clinical study on immunotherapy of reporting coagulation disorders.
