VTE risk with checkpoint inhibitors

Cancer patients treated with immune checkpoint inhibitors have been shown to have an increased risk of venous thromboembolism (VTE) and a poorer prognosis.

A retrospective Austrian study of 673 patients treated with a checkpoint inhibitor between 2015 and 2018 found 12.9% developed a VTE over a median follow-up period of 8.5 months..

Patients had a range of cancers including mostly melanoma (30%), non-small cell lung cancer (24%), renal cell carcinoma (11%), and head and neck squamous cell carcinoma (10%).

Their treatments included mostly nivolumab (42%), pembrolizumab (40%), ipilimumab (6.7%), a combination of ipilimumab and nivolumab (6%), and others.

The study found the occurrence of VTE – including PE (n=18), DVT (n=17), catheter-related thrombosis (n=4) and visceral vein thrombosis (n=5) – was associated with a shorter progression-free survival (HR 3.63) and a shorter overall survival (HR 3.09).

The mean OS after the occurrence of VTE was 11.6 months compared to 25.5 months in patients without VTE.

As well, the study found the incidence of arterial thromboembolism (ATE) – acute coronary syndrome, ischaemic stroke and acute vascular occlusions – was 1.8% in patients treated with checkpoint inhibitors.

However the study, published in Blood, found ATE was not associated with the risk of mortality or early progression of disease.

There was no difference in VTE risk between subgroups of patients based on their tumour type or their particular checkpoint inhibitor therapy.

The study said the diagnosis of VTE led to a brief disruption of therapy in some patients. ATE frequently resulted in a substantial delay in treatment and led to treatment discontinuation in one patient.

The only significant risk factor for VTE was a history of a previous VTE.

The investigators said the “substantial risk” of VTE and ATE could be related to factors such as advanced stage of disease, long-term survival compared to the pre-checkpoint inhibitor era or treatments received prior to checkpoint inhibitors.

“Mechanistically, a systemic proinflammatory status, induced by immune checkpoint inhibitors, might enhance the prothrombotic state by activation of coagulation, platelets and impairment of fibrinolysis,” they said.

“Whether the observed risk of VTE and ATE under therapy with immune checkpoint inhibitors is increased by this new type of oncologic treatment itself or just reflects the baseline risk of patients cannot be answered at this stage, as comparisons with a control group without immune checkpoint inhibitor therapy comprising similar cancer types, stage and level of pre-treatment are currently not available.”

The researchers said further studies on the specific risk factors for VTE and ATE and the clinical consequences in the context of immune checkpoint inhibitor therapy were warranted.

“Especially given the possibility of long-term treatment response and improved survival with immune checkpoint inhibitor therapy, the identification of secondary causes of morbidity and mortality, including VTE and ATE, are of utmost importance, irrespective of potential causality.”

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