medwireNews: Prophylactic treatment with apixaban is not associated with a significant reduction in the risk for venous thromboembolism (VTE) relative to no systemic anticoagulation in pediatric patients with acute lymphoblastic leukemia or lymphoma (ALL/LBL), indicate trial data.
But the researchers point out in The Lancet Haematology that use of the direct oral anticoagulant did not increase the risk for major bleeding and the drug “can be considered safe.”
They continue: “Based on the results of PREVAPIX-ALL, apixaban cannot be recommended for routine thromboprophylaxis.
“However, with apixaban’s safety profile, paediatric formulation, and ease of administration, its use could be considered when thromboprophylaxis is desired for paediatric patients with acute lymphoblastic leukaemia or lymphoma who have an increased risk of venous thromboembolism.”
In the phase 3 study, 512 patients (1 year to <18 years) with newly diagnosed ALL or LBL and a central venous line in place throughout induction therapy were randomly assigned to receive weight-adjusted apixaban or no systemic anticoagulation (standard of care). Participants weighing 35 kg or less were given apixaban at a dose of 2.5 mg twice daily, while those weighing more than 35 kg received weight-adjusted prophylactic doses twice daily.
At a median follow-up of 27 days, the primary efficacy endpoint – a composite of symptomatic or clinically unsuspected VTE – occurred in 12% of patients in the apixaban group and 18% of those in the control group, where the between-group difference was not statistically significant.
“There are several possible reasons why our findings did not achieve statistical significance, with the most likely causes being the short study timeframe and limited exposure to the study intervention,” say Sarah O’Brien (Nationwide Children’s Hospital and The Ohio State University, Columbus, USA) and team.
The primary safety outcome was major bleeding, and there were two events in each group.
However, the secondary safety outcome of clinically relevant nonmajor (CRNM) bleeding was significantly more common in the apixaban than control arm, at rates of 4% versus 1%, and a relative risk of 3.67.
“The imbalance was predominantly due to an increased incidence of CRNM epistaxis,” say the investigators.
Of note, a post-hoc analysis by age showed that the incidence of major or CRNM bleeding was higher with apixaban than no anticoagulation among patients younger than 10 years (4 vs 1%), but not among those aged 10 years or older (6 vs 5%).
The author of an accompanying commentary notes that several studies have shown that the incidence of VTE is lowest in children aged younger than 5 years and highest in those aged 15–18 years.
Uma Athale (McMaster University, Hamilton, Ontario, Canada) therefore says: “These observations beg the question: why subject younger children to the potential harm of bleeding?
“Why not give the intervention to only patients aged 10 years or older, or patients categorised as having high-risk acute lymphoblastic leukaemia (who receive more intensified therapy)?”
She concludes that “[a]lthough there is no question that thromboembolisms associated with acute lymphoblastic leukaemia need to be prevented, judicious use of anticoagulation is also warranted.”
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Lancet Haematol 2023; doi:10.1016/S2352-3026(23)00314-9
Lancet Haematol 2023; doi:10.1016/S2352-3026(23)00339-3