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Randomized Controlled Trial
. 2025 Sep 23;9(18):4738-4747.
doi: 10.1182/bloodadvances.2025016160.

Safety and efficacy of apixaban thrombosis prevention in pediatric patients with obesity and acute lymphoblastic leukemia

Vilmarie Rodriguez  1 , Sarah H O'Brien  1 , Etan Orgel  2   3 , Corinna L Schultz  4 , Adam J Esbenshade  5 , Arteid Memaj  6 , Joshua L Dyme  7 , Nicholas A Favatella  7 , Lesley G Mitchell  8
Affiliations
Randomized Controlled Trial

Safety and efficacy of apixaban thrombosis prevention in pediatric patients with obesity and acute lymphoblastic leukemia

Vilmarie Rodriguez et al. Blood Adv. .

Abstract

Pediatric patients with acute lymphoblastic leukemia and lymphoma (ALL/LL) and obesity are at increased risk for venous thromboembolism (VTE). The PREVAPIX-ALL trial was an open-label, randomized, controlled trial assessing the safety and efficacy of apixaban for VTE prevention in pediatric patients with ALL/LL. An a priori subgroup analysis of patients with obesity in the PREVAPIX-ALL trial was planned because of increased VTE risk in this group. Patients with obesity, aged ≥2 to <18 years, central venous catheter, and chemotherapy containing asparaginase were randomized to apixaban (prophylactic dose) vs standard of care (SOC; no anticoagulation) during induction chemotherapy. The primary efficacy end point was a composite of nonfatal symptomatic and asymptomatic VTE and VTE-related death. The primary and secondary safety outcomes were major bleeding and a composite of major and clinically relevant nonmajor (CRNM) bleeding, respectively. A total of 82 PREVAPIX-ALL participants presented with obesity, of whom 42 were randomized to apixaban. For the primary efficacy end point, a significant decrease in VTE events was present in the apixaban arm (1/42 [2.4%]) as compared with the SOC arm (10/40 [25%]; relative risk [RR], 0.09; 95% confidence interval [CI], 0.01-0.97; P = .007). There was a statistically significant treatment obesity interaction, P = .03. No statistically significant difference was observed for the primary efficacy end point among the nonobese group (RR, 0.85; 95% CI, 0.53-1.37; P = .50). No statistically significant difference in major or CRNM bleeding was observed. Apixaban prophylaxis in patients with obesity and ALL/LL resulted in a statistically significant VTE risk reduction with no increase bleeding. This trial was registered at www.clinicaltrials.gov as #NCT02369653.

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Conflict of interest statement

Conflict-of-interest disclosure: A.M., J.L.D., and N.A.F. are employees of Bristol Myers Squibb (BMS). The institutions of V.R. and S.H.O. received salary support from the Children’s Oncology Group for their roles as study chair and study vice-chair, respectively. E.O. served as a consultant for Jazz Pharmaceuticals; and received consulting fees from Seagen, Inc. L.G.M. received research funding from BMS for the biomarker substudy. The remaining authors declare no competing financial interests.

A complete list of the PREVAPIX-ALL investigators appears in “Appendix.”

Figures

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Graphical abstract
Figure 1.
Figure 1.
CONSORT diagram. Summary randomization.
Figure 2.
Figure 2.
Comparison of Apixaban median steady state AUC (TAU). Comparison of the median steady-state AUC (TAU) in pediatric patients without vs those with obesity, stratified by age (A) and weight on a linear scale (B). AUC, area under the curve; TAU, TAU(dosing interval)
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References

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