OC 61.5 - Immune tolerance induction in patients with hemophilia A and high-titer inhibitors with emicizumab prophylaxis

Tuesday, June 25, 2024

15:45 – 16:00 ICT

Room: Ballroom B1

Co-Author(s)

Carolina Costa-Lima

Hematologist
Hemocentro UNICAMP, University of Campinas, Campinas, SP, Brazil
Campinas, Sao Paulo, Brazil
VF

Vanessa B Faiotto

Study coordinator
Hemocentro UNICAMP, University of Campinas, Campinas, SP, Brazil
Campinas, Sao Paulo, Brazil
Jéssica O. Frade-Guanaes

Post doctoral
Hemocentro UNICAMP, University of Campinas, Campinas, SP, Brazil
Campinas, Sao Paulo, Brazil
AF

Ana P. Francisco

Laboratory technologist
Hemocentro UNICAMP, University of Campinas, Campinas, SP, Brazil
Campinas, Sao Paulo, Brazil
NF

Nívia M. Foschi

Hematologist
Hemocentro UNICAMP, University of Campinas, Campinas, SP, Brazil
Campinas, Sao Paulo, Brazil
AS

Andrea L. A. Sambo

Nurse
Hemocentro UNICAMP, University of Campinas, Campinas, SP, Brazil
Campinas, Sao Paulo, Brazil
MH

Mariana M. T. Hosokawa

Nurse
Hemocentro UNICAMP, University of Campinas, Campinas, SP, Brazil
Campinas, Sao Paulo, Brazil
VS

Valdirene C. Stahl

Nurse
Hemocentro UNICAMP, University of Campinas, Campinas, SP, Brazil
Campinas, Sao Paulo, Brazil
SM

Samuel S Medina

Hematologist
Hemocentro UNICAMP, University of Campinas, Campinas, SP, Brazil
Campinas, Sao Paulo, Brazil
MC

Marina P. Collela

Hematologist
Hemocentro UNICAMP, University of Campinas, Campinas, SP, Brazil
Campinas, Sao Paulo, Brazil
Silmara A. De Lima-Montalvão

Biologist
Hemocentro UNICAMP, University of Campinas, Campinas, SP, Brazil
Campinas, Sao Paulo, Brazil
Gabriela G. Yamaguti-Hayakawa

Hematologist
Hemocentro Unicamp, Universidade de Campinas (Unicamp), Campinas, SP, Brasil
Campinas, Sao Paulo, Brazil

Presenting Author(s)

Margareth C. Ozelo, MD, PhD

Professor
Hemocentro UNICAMP, Department of Internal Medicine, School of Medical Sciences, University of Campinas
Campinas, Sao Paulo, Brazil

Background: Immune tolerance induction (ITI) is the treatment for eradicating inhibitors in hemophilia A (HA) patients, thereby reinstating the efficacy of factor VIII (FVIII) replacement therapy. Nevertheless, ITI typically requires an extended duration, during which frequent bleeding episodes are often observed while the inhibitors remain active.

Aims: This prospective study aims to evaluate the efficacy of low-dose ITI along with emicizumab prophylaxis.

Methods: HA patients with high-titer FVIII inhibitors and no previous ITI treatment were included in this study. Following a four-week emicizumab loading dose (3mg/kg), participants commenced low-dose ITI (FVIII 50IU/kg, 3x/wk) alongside emicizumab maintenance dose (1.5mg/kg/wk). Upon achieving immunotolerance, patients were maintained on emicizumab prophylaxis for an additional year, complemented by a reduced FVIII dosage of 25IU/kg once a week.

Results: Ten participants, including nine children, were enrolled between August 2021 and February 2023 (Table 1). Five (50%) patients have already reached the complete success criteria for ITI. One patient has a confirmed negative inhibitor titer but no recovery criteria for response. The median time the six patients reached negative inhibitors was 19.5 weeks (2-90 weeks). Two patients have a low-titer positive FVIII inhibitor ( < 2 BU/ml) after 16 and 42 weeks of ITI. Two patients on ITI remain with high inhibitor titers but below 7BU/ml (Figure 1). After 18 months of ITI, two patients increased the FVIII dose (100 IU/kg daily and 3x/wk). The median annualized treated bleeding rate (ABR) decreased from 4 bleeds/year (range 2-28) before ITI initiation to 0 (0-2.4) during the ITI period (p = 0.002).

Conclusion(s): Preliminary findings from this prospective ITI protocol and emicizumab prophylaxis demonstrate promising outcomes. Notably, 60% of patients completing at least 44 weeks of the first ITI attempt achieved negative inhibitors, with 50% attaining complete ITI success. As expected, initiating emicizumab prophylaxis was associated with significantly reducing bleeding episodes.