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Randomized Controlled Trial
. 2022 Nov 22;6(22):5821-5828.
doi: 10.1182/bloodadvances.2022008160.

Anticoagulation in pediatric cancer-associated venous thromboembolism: a subgroup analysis of EINSTEIN-Jr

Joseph S Palumbo  1 , Anthonie W A Lensing  2 , Leonardo R Brandão  3 , Hélène L Hooimeijer  4 , Gili Kenet  5   6 , Heleen van Ommen  7 , Akos F Pap  2 , Madhurima Majumder  8 , Dagmar Kubitza  2 , Kirstin Thelen  2 , Stefan Willmann  2 , Martin H Prins  9 , Paul Monagle  10   11 , Christoph Male  12
Affiliations
Randomized Controlled Trial

Anticoagulation in pediatric cancer-associated venous thromboembolism: a subgroup analysis of EINSTEIN-Jr

Joseph S Palumbo et al. Blood Adv. .

Abstract

Anticoagulant treatment of pediatric cancer-associated venous thromboembolism (VTE) has not been prospectively evaluated. Management of anticoagulation for cancer-associated VTE is often challenged by drug interactions and treatment interruptions. A total of 56 of the 500 children (11.2%) with VTE who participated in the recent EINSTEIN-Jr randomized study had cancer (hematologic malignancy, 64.3%, solid malignant tumor, 35.7%). Children were allocated to either therapeutic-dose bodyweight-adjusted oral rivaroxaban (n=40) or standard anticoagulation with heparins, with or without vitamin K antagonists (n=16) and received a median of 30 concomitant medications. Based on sparse blood sampling at steady-state, pharmacokinetic (PK) parameters of rivaroxaban were derived using population PK modeling. During the 3 months of treatment, no recurrent VTE or major bleeding occurred (95% confidence interval, 0.0%-6.4%), and 3-month repeat imaging showed complete or partial vein recanalization in 20 and 24 of 52 evaluable children (38.5% and 46.2%, respectively). Anticoagulant treatment was interrupted 70 times in 26 (46.4%) children because of thrombocytopenia, invasive procedures, or adverse events, for a mean individual period of 5.8 days. Anticoagulant therapy was resumed in therapeutic doses and was not associated with thrombotic or bleeding complications. Rivaroxaban exposures were within the adult exposure range and similar to those observed in children with VTE who did not have cancer-associated VTE. Rivaroxaban and standard anticoagulants appeared safe and efficacious and were associated with reduced clot burden in most children with cancer-associated VTE, including those who had anticoagulant treatment interruptions. Rivaroxaban exposures were within the adult exposure range despite significant polypharmacy use. This trial was registered at www.clinicaltrials.gov as #NCT02234843.

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Conflict of interest statement

A.W.A.L., A.F.P., M.M., D.K., S.W., and K.T. are the employees of Bayer. C.M. reports personal fees and fees paid to his institution from Anthos, Bayer, Bristol-Myers Squibb, Janssen, Norgine, Pfizer, and Boehringer Ingelheim. H.v.O. reports fees paid to her institution from Bayer, Boehringer Ingelheim, and Octopharma. G.K. reports personal fees and fees paid to her institution from Bayer and Pfizer. The remaining authors declare no competing financial interests.

Figures

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Graphical abstract
Figure 1
Figure 1
Flowchart of selection of patients for the EINSTEIN-Jr cancer substudy.
Figure 2
Figure 2
Rivaroxaban population PK modeling results for children with cancer-associated VTE in comparison with adult patients with VTE and children with VTE without cancer. od, once daily; PopPK, population PK.
See this image and copyright information in PMC

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References

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