PREVAPIX-ALL: Phase 3 Study of The Safety and Afficacy of Apixaban for Thromboprophylaxis Versus Standard of Care in Newly Diagnosed Pediatric Acute Lymphoblastic Leukemia or Lymphoma (ALL/LL)
Author Type(s)
Faculty
Document Type
Abstract
Publication Date
2022
Journal Title
Research and Practice in Thrombosis and Haemostasis
Department
Pediatrics
Abstract
Background: Pediatric patients with ALL/LL are at increased risk of venous thromboembolism (VTE). Aims: To assess efficacy and safety of prophylactic apixaban vs. standard-of-care (SOC) for VTE prevention during induction chemotherapy. Methods: Following ethics committee approval and informed consent patients ≥1 to <18 years with (1) newly diagnosed ALL/LL, (2) central venous line, and (3) three or four drug induction chemotherapy with asparaginase, were randomized in an open label, randomized controlled trial conducted in collaboration with the Children's Oncology Group. Apixaban thromboprophylaxis was stopped at the end of induction (Figure). After induction, patients underwent VTE screening. The primary efficacy endpoint was a composite of symptomatic/ asymptomatic VTE and VTE-related death. The primary safety endpoint was major bleeding. Results: 512 patients (56.5% male, mean age 7.2 years) were randomized. VTE occurred in 12.1% (n = 31) of apixaban patients and 17.6% (n = 45) of SOC patients (Table). No differences were shown in the primary efficacy endpoint between study arms [RR: 0.69 (0.45-1.05), 1-sided p-value 0.04]. In obese patients (n = 82), 1 VTE occurred in the apixaban arm vs. 10 in the SOC arm [RR: 0.11 (0.02-0.74), treatment-subgroup interaction p-value 0.036]. There were 2 major bleeding events in each arm (including 1 event before treatment with apixaban). A numerically higher incidence of clinically relevant non-major bleeding occurred in the apixaban arm (11 vs. 3 events) due to increased epistaxis. Conclusion(s): PREVAPIX-ALL is the first trial to assess primary prophylaxis using a direct oral anticoagulant in pediatric ALL/LL. Apixaban was not shown to be efficacious in the primary analysis but decreased VTE risk in obese patients. Major and clinically relevant non-major bleeding was infrequent. No new safety signals were observed. Apixaban was found to be a safe pharmacologic prophylaxis agent in pediatric patients with ALL/LL receiving induction chemotherapy containing asparaginase.
Recommended Citation
O'Brien, S., Rodriguez, V., Lew, G., Newburger, J., Schultz, C., Orgel, E., Derr, K., Ranalli, M., Esbenshade, A., Hochberg, J., Kang, H., Dinikina, Y., Crevar, C., Donovan, M., Dyme, J., Favatella, N., & Mitchell, L. (2022). PREVAPIX-ALL: Phase 3 Study of The Safety and Afficacy of Apixaban for Thromboprophylaxis Versus Standard of Care in Newly Diagnosed Pediatric Acute Lymphoblastic Leukemia or Lymphoma (ALL/LL). Research and Practice in Thrombosis and Haemostasis, 6. https://doi.org/10.1002/rth2.12787
