OC 15.1 - PREVAPIX-ALL: Phase 3 Study of the Safety and Efficacy of Apixaban for Thromboprophylaxis versus Standard of Care in Newly Diagnosed Pediatric Acute Lymphoblastic Leukemia or Lymphoma (ALL/LL)

Sunday, July 10, 2022

10:45 AM – 11:00 AM

Location: ExCel Center, ICC Capital Suite Room 14-16

Presentation Format: In-Person

Presenting Author(s)

Sarah H. O'Brien, MD, MSc

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

Co-Author(s)

VR

Vilmarie Rodriguez

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

Glen Lew

Senior Clinical Trial Physician
Bristol Myers Squibb, Inc
Summit, New Jersey, United States
JN

Jane W. Newburger

Commonwealth Professor of Pediatrics
Department of Cardiology, Boston Children's Hospital & Department of Pediatrics, Harvard Medical School
Boston, Massachusetts, United States
CS

Corinna L. Schultz

Associate Professor of Pediatrics
Nemours Center for Cancer and Blood Disorders, Nemours Children's Health
Wilmington, Delaware, United States
EO

Etan Orgel

Associate Professor of Clinical Pediatrics
Cancer and Blood Disease Institute, Children's Hospital Los Angeles
Los Angeles, California, United States
KD

Kimberly Derr

Clinical Research Coordinator
Department of Pediatric Oncology, Geisinger
Danville, Pennsylvania, United States
MR

Mark A. Ranalli

Associate Professor
Division of Pediatric Hematology/Oncology, Nationwide Children's Hospital & The Ohio State University
Colulmbus, Ohio, United States
AE

Adam J. Esbenshade

Associate Professor
Monroe Carell Jr. Children's Hospital at Vanderbilt, Vanderbilt University Medical Center
Nashville, Tennessee, United States
JH

Jessica J. Hochberg

Associate Professor
Department of Pediatrics, New York Medical College
Valhalla, New York, United States
HK

Hyoung J. Kang

Professor
Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Cancer Research Institute& Wide River Institute of Immunology, Seoul National University Children's Hospital
Seoul, Kyonggi-do, Republic of Korea
YD

Yulia Dinikina

Associate Professor
Department of Chemotherapy for Oncohematological Diseases and Bone Marrow Transplantation for Children, Almazov National Medical Research Centre
Saint Petersburg, Saint Petersburg City, Russia
CC

Christina T. Crevar

Global Trial Manager
Bristol Myers Squibb, Inc.
Lawrence Township, New Jersey, United States
MD

Mark Donovan

Senior Director of Biostatistics
Bristol Myers Squibb, Inc.
Lawrence Township, New Jersey, 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
LM

Lesley G. Mitchell, MD

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

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.