OC 38.3 - Effects of Apixaban Versus No Anticoagulation on Biomarkers of Thrombin Generation in Pediatric Acute Lymphoblastic Leukemia (ALL): A Biomarker Sub-study of PREVAPIX-ALL, a Randomized Controlled Trial

Monday, June 26, 2023

11:15 – 11:30 ET

Room: 518

Session Available As: On-Demand

Co-Author(s)

KD

Kevin Dietrich

Ex-Senior Laboratory Technician (deceased)
University of Alberta, Division of Pediatric Hematology/Oncology
Edmonton, Alberta, Canada
ZW

Zhaoqing Wang

Sr. Director
Bristol Myers Squibb
Lawrence Township, New Jersey, United States
JL

Jessica Landis

Senior Principal Scientist
Bristol Myers Squibb
Lawrence Township, New Jersey, United States
TY

Tejaswi Yarra

Consultant/Associate Scientific Director
Bristol Myers Squibb/Parexel
Lawrence Township, New Jersey, United States
SO

Sarah O'Brien

Associate Professor and Director or Experimental Therapeutics
Nationwide Children's Hospital
Columbus, Ohio, United States
VR

Vilmarie Rodriguez

Professor
Division of Hematology/Oncology/BMT, Nationwide Children's Hospital
Columbus, Ohio, United States
JD

Joshua L. Dyme

Senior Clinical Trial Physician
Bristol Myers Squibb
Lawrence Township, New Jersey, United States
NF

Nicholas A. Favatella

Lead Clinical Scientist
Bristol Myers Squibb
Lawrence Township, New Jersey, United States
AH

Aiqing He

Principal Scientist
Bristol Myers Squibb
Lawrence Township, New Jersey, United States

Presenting Author(s)

Lesley G. Mitchell, Professor

Professor
University of Alberta, Division of Pediatric Hematology/Oncology
Edmonton, Alberta, Canada

Background: Pediatric patients being treated for ALL are at increased risk for venous thromboembolism (VTE) during induction chemotherapy which is associated with a hypercoagulable state. Apixaban decreases activation of the procoagulant pathway. PREVAPIX-ALL study assessed safety and efficacy of apixaban versus no anticoagulation (SOC) at reducing VTE in pediatric ALL patients and offered an unprecedented opportunity to assess anticoagulant effect of apixaban in children.

Aims: To better understand the anticoagulant effect of apixaban in pediatric ALL patients during induction chemotherapy by measuring a comprehensive panel of hemostatic biomarkers.

Methods: Plasma samples were obtained from 191 consented PREVAPIX-ALL participants (n=81 randomised to apixaban; n=110 randomised to SOC) at baseline, Days 8, 15, 22 and 29 of induction chemotherapy. D-Dimer, Prothrombin F1.2 (F1.2), thrombin-antithrombin complex (TAT), Thrombin generation assay (TGA) and fibrin generation capacity (FGC) were assessed.

Results: D-dimer, F1.2 and TAT decreased during induction chemotherapy in both arms. However, apixaban arm had a significantly greater decrease when compared to SOC (Figure 1). Peak thrombin decreased from baseline in both arms, but to a greater extent for apixaban versus SOC at Days 15 and 22. Endogenous thrombin potential was not changed by SOC and decreased by apixaban at Day 22. The SOC arm had a significant decrease in fibrin lag time to 50% clot and lag time to thrombin generation indicating a procoagulant state; both lag times were significantly increased in the apixaban arm (Figure 2).

Conclusion(s): Treatment with apixaban significantly decreased F1.2, TAT and D-dimer, which are markers of a hypercoagulable state, when compared to SOC. Time to thrombin and fibrin generation were shortened in the SOC arm indicating a procoagulant state and apixaban lengthened these times indicating a decrease in the prothrombotic state. Apixaban decreases the hypercoagulable state, as indicated by these biomarkers, in children with ALL undergoing induction chemotherapy.

Funding: Bristol Myers Squibb/Pfizer Alliance

Learning Objectives:

Describe the design of the PREVAPIX-ALL trial and the design of the PREVAPIX-ALL biomarker sub-study
Describe the pattern of levels of biomarkers of thrombin and plasmin generation during induction chemotherapy in children treated with apixaban versus standard of care in children with acute lymphoblastic leukemia (ALL)
Describe the pattern of functional thrombin generation and fibrin generation assays during induction chemotherapy comparing children treated with apixaban versus standard of care in children with ALL