Apixaban fails to check VTE among children with lymphocytic leukemia

Acute lymphocytic leukemia is the most common type of cancer in children, and treatments result in a good chance for a cure. However complications are more threatening and managing them becomes a priority especially in pediatric patients. Reportedly kids with acute lymphoblastic leukaemia or lymphoma are at increased risk of venous thromboembolism resulting in increased mortality and morbidity.

The new trial PREVAPIX-ALL is, the first trial assessing primary thromboprophylaxis using a direct oral anticoagulant in paediatric patients with acute lymphoblastic leukaemia or lymphoma according to the authors. The trial reports that there was no statistically significant treatment benefit identified in participants receiving apixaban. Major and clinically relevant non-major (CRNM) bleeding were infrequent overall, but a higher incidence of CRNM bleeding (primarily epistaxis in younger children) occurred in participants receiving apixaban. The findings are published in The Lancet Hematology.

Researchers in the phase 3, open-label, randomised, controlled trial conducted in 74 paediatric hospitals in 9 countries. Participants aged 1 year or older to younger than 18 years with newly diagnosed acute lymphoblastic leukaemia (pre-B cell or T cell) or lymphoblastic lymphoma (B cell or T cell immunophenotype) and a central venous line in place throughout induction were randomly assigned 1:1 to standard of care (SOC, ie, no systemic anticoagulation) or weight-adjusted twice-daily apixaban during induction. Randomisation was performed centrally and stratified by age (those <10 years or those ≥10 years).

Participants weighing 35 kg or less were administered 2•5 mg twice daily of apixaban as a 2•5 mg tablet, 0•5 mg tablets, or 0•4 mg/mL oral solution, while those weighing more than 35 kg were administered weight-adjusted prophylactic doses using 0•5 mg tablets or the 0•4 mg/mL oral solution twice daily. Primary outcomes were assessed by a blinded central adjudication committee. The primary efficacy outcome for the intention to treat population was the composite of symptomatic or clinically unsuspected venous thromboembolism, the primary safety outcome was major bleeding, and secondary safety outcomes included clinically relevant non-major (CRNM) bleeding. Patients were screened for venous thromboembolism by ultrasound and echocardiogram at the end of induction.

The key findings of the study are

• A total of 512 participants were randomly assigned and included in analyses (222 [43%] female and 290 [57%] male; 388 [76%] White, 52 [10%] Asian, 24 [5%] Black or African American, and 48 [9%] other races; and 122 [24%] Hispanic or Latino ethnicity).

• During a median follow-up period of 27 days, 31 (12%) of 256 patients on apixaban had a composite venous thromboembolism compared with 45 (18%) of 256 participants receiving SOC.

• Two major bleeding events occurred in each group. A higher incidence of CRNM bleeding, primarily grade 1 or 2 epistaxis, occurred in the apixaban group (11 [4%] of 256 participants) compared with the SOC group.

• The most frequent grade 3–5 adverse events in both groups were thrombocytopenia, 28 for the apixaban group and 20 for the SOC group or platelet count decreased in 49 and 45, anaemia in 77 and 74, febrile neutropenia in 27 and 20, and neutropenia in 16 and 17 or neutrophil count decreased in 22 and 25.

• Five deaths occurred, which were due to infection (3 in the SOC group), cardiac arrest (1 in apixaban group), and haemorrhagic cerebral sinus vein thrombosis (1 in the SOC group). There was one apixaban-related death (coagulopathy and haemorrhage after cardiac arrest of unknown cause).

Researchers concluded that “PREVAPIX-ALL is, to our knowledge, the first trial assessing primary thromboprophylaxis using a direct oral anticoagulant in paediatric patients with acute lymphoblastic leukaemia or lymphoma. No statistically significant treatment benefit was identified in participants receiving apixaban. Major and CRNM bleeding were infrequent overall, but a higher incidence of CRNM bleeding (primarily epistaxis in younger children) occurred in participants receiving apixaban. For patients deemed to be at particularly high risk of thrombosis, PREVAPIX-ALL provides encouraging safety data for the use of apixaban in clinical settings in which the potential benefits are thought to outweigh the risk of bleeding.”

Reference: Sarah H O'Brien, MD , Prof Vilmarie Rodriguez, MD, Glen Lew, MD, Prof Jane W Newburger, MD; Apixaban versus no anticoagulation for the prevention of venous thromboembolism in children with newly diagnosed acute lymphoblastic leukaemia or lymphoma (PREVAPIX-ALL): a phase 3, open-label, randomised, controlled trial; DOI :https://doi.org/10.1016/S2352-3026(23)00314-9.