OC 61.2 - Determinants of successful immune tolerance induction in people with severe hemophilia A

Tuesday, June 25, 2024

15:00 – 15:15 ICT

Room: Ballroom B1

Presenting Author(s)

Ilja Oomen, MD

MD
Department of Pediatric Hematology, Amsterdam UMC location University of Amsterdam, Meibergdreef 9, Amsterdam, the Netherlands
Amsterdam, Noord-Holland, Netherlands

Co-Author(s)

Ricardo Mesquita Camelo, MD, MBA, MSc, PhD, PostD

Professor
Department of Internal Medicine, Faculty of Medicine, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil
Belo Horizonte, Minas Gerais, Brazil
Manuel Carcao

Professor
Department of Pediatrics, Division of Hematology/Oncology, Hospital for Sick Children, Toronto, Canada
Toronto, Ontario, Canada
Giancarlo Castaman

Medical Director Hematologist
Department of Oncology Careggi University Hospital, Florence, Italy
Florence, Toscana, Italy
Kathelijn Fischer

Pediatric Hematologist
Centre for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands
Utrecht, Utrecht, Netherlands
Frank W.G Leebeek, MD PhD

Internist-hematologist, Professor
Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands
Rotterdam, Zuid-Holland, Netherlands
David Lillicrap, MD

Professor Department of Pathology and Molecular Medicine
Molecular Hemostasis Research Group, Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.
Kingston, Ontario, Canada
Maria Elisa Mancuso, MD, PhD

Senior Consultant in Haematology
Centre for Thrombosis and Haemorrhagic Diseases, IRCCS Humanitas Research Hospital
Milan, Lombardia, Italy
Davide Matino

Assistant Professor
Division of Hematology & Thromboembolism, Department of Medicine, McMaster University, Ontario, Canada
Hamilton, Ontario, Canada
MD

Matteo Di Minno

Professor
Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy
Naples, Campania, Italy
AM

Alexander Mohseny

MD
Department of Pediatric Hematology, Leiden University Medical Center, Leiden, the Netherlands
Leiden, Zuid-Holland, Netherlands
Johannes Oldenburg, MD

Professor, Chairman and Director
University Clinic Bonn AöR, Institute of Experimental Haematology and Transfusion Medicine
Bonn, Nordrhein-Westfalen, Germany
Suely M. Rezende, MD, PhD

Professor of Internal Medicine
Universidade Federal de Minas Gerais
Belo Horizonte, Minas Gerais, Brazil
GR

Georges-Etienne Rivard

MD
Department of Pediatrics, Division of Hematology-Oncology, Montréal University, CHU Sainte-Justine, Montréal, Québec, Canada
Montréal, Quebec, Canada
NR

Natalia Rydz

Assistant Professor
Department of Medicine, Division of Hematology, University of Calgary, Calgary, Alberta, Canada
Calgary, Alberta, Canada
SS

Saskia E.M. Schols

Internist-hematologist
Department of Hematology, Radboud university medical center, Nijmegen, The Netherlands
Nijmegen, Gelderland, Netherlands
JV

Jan Voorberg

Professor
Department of Molecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam, the Netherlands
Amsterdam, Noord-Holland, Netherlands
KF

Karin Fijnvandraat

Professor
Emma Kinderziekenhuis/AMC, University of Amsterdam, Netherlands
Amsterdam, Noord-Holland, Netherlands
SG

Samantha C. Gouw, MD PhD

Pediatric hematologist
Department of Pediatric Hematology, Emma Children’s Hospital, Amsterdam UMC location University of Amsterdam, Amsterdam, the Netherlands
Amsterdam, Noord-Holland, Netherlands
Jeroen Eikenboom

MD, PhD, prof
Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands
Leiden, Zuid-Holland, Netherlands

Background: Inhibitor eradication to restore factor VIII (FVIII) efficacy is a desirable treatment goal for persons with severe hemophilia A (SHA) and inhibitors. This enables treatment of bleeding episodes with FVIII concentrates rather than relying on bypassing agents which are less effective. However, since immune tolerance induction (ITI) is burdensome, costly and not always successful, it is important to identify determinants for ITI success to maximize effective resource allocation. This has never been more crucial than now with the availability of emicizumab.

Aims: We aim to identify determinants of successful ITI in persons with SHA.

Methods: European, Brazilian, and Canadian persons with SHA who underwent ITI were recruited. The primary outcome was clinical ITI success, defined by (1) a negative inhibitor titer, and (2) an adequate clinical response to FVIII concentrates. Clinical determinants included F8 genotype, ethnicity, age at inhibitor development/ITI initiation, number of FVIII exposure days before inhibitor development, inhibitor titers, and ITI regimen. Genetic determinants included FCGR gene, IL10 CA short tandem repeat, and gene variants included in the Global Screening Array. Odds ratios were calculated for ITI success with 95% confidence intervals.

Results: In total, 224 persons with SHA were included. Baseline characteristics are presented in Table 1. Historical peak titer < 50 BU/mL was strongly associated with ITI success, as compared to ≥50 BU/mL (Figure 1). Determinants associated with ITI success were ITI initiation < 1 month from inhibitor development and inhibitor titers (at detection/pre-ITI) < 10 BU/mL, compared to respectively ≥1 month and ≥10 BU/mL. The presence of a central venous access device infection and FVIII exposure days < 15 (versus ≥15) before inhibitor development were negative predictors for ITI success.

Conclusion(s): Inhibitor titers (at detection/pre-ITI/historical peak), and total FVIII exposure days before inhibitor development were associated with ITI success. Other clinical determinants were not clearly associated with ITI outcome.