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Higher thrombotic risk in NSCLC patient with ALK rearrangement

Presented by
Dr Hanny Al-Samkari, Massachusetts General Hospital, USA
ISTH 2020


A retrospective observational study showed that anaplastic lymphoma kinase gene (ALK) rearrangement in lung cancer patients is associated with a 3 to 4 times elevated thrombotic risk compared with ALK-negative lung cancer patients [1].

Chromosomal translocations involving ALK are rare oncogenic events found in 3-5% of non-small-cell lung cancers (NSCLC). Prior studies have shown that ALK rearrangement in NSCLC patients might confer an elevated risk for cancer-associated venous thromboembolism (VTE). Dr Hanny Al-Samkari (Massachusetts General Hospital, USA) and colleagues compared the risk for VTE and arterial thrombosis of 400 NSCLC patients with ALK rearrangement with 800 NSCLC patients without ALK rearrangement who were treated between 2009 and 2019. They performed multivariable time-to-event analysis to assess the risk of first venous or arterial thrombosis in both groups and controlled for covariates that impact thrombotic risk, e.g. known thrombophilia, in the VTE model.

Dr Al-Samkari pointed out that the ALK group had more favourable characteristics compared with the non-ALK group. ALK patients were considerably younger (mean age 50 vs 66 years; P<0.001), significantly fitter with 87.2% of ALK patients having an ECOG performance status 1 or 2 vs 54.1% of the non-ALK group. In addition, patients in the ALK group smoked much less (29.9% vs 77.1%) and had significantly lower or similar rates of other VTE risk factors (e.g. brain metastases, obesity, prior VTE). The ALK group also had significantly lower rates of other arterial thrombosis risk factors such as hypertension, hyperlipidaemia, atherosclerosis, diabetes, or atrial fibrillation. Despite these differences, the initial overall VTE rate was significantly higher (42.7%) in the ALK group compared with the non-ALK group (28.6%). Likewise, the rate of recurrent VTE was significantly elevated in the ALK-group (13.5% vs 3.1%). Despite significantly lower rates of all major arterial thrombosis risk factors, arterial thrombosis rates were similar in the 2 groups (5.0% vs 4.4%). In addition, the VTE-free survival was lower than in the non-ALK group.

“Keep in mind that the ALK group was nearly 2 decades younger and had far fewer risk factors. Despite these differences, they had a 4-fold increase in VTE risk and a 3-fold increase in arterial thrombosis risk in NSCLC,” Dr Al-Samkari explained. Therefore, patients with NSCLC harbouring an ALK rearrangement may have a distinct benefit from the use of pharmacologic thromboprophylaxis.

    1. Al-Samkari H, et al. OC 10.2.ISTH 2020 Virtual Congress, 12-14 July.


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