OC 43.5 - Should immune tolerance be pursued in the era of Emicizumab? Longitudinal follow up of a FVIII inhibitor cohort - Real World Data

Monday, June 26, 2023

15:45 – 16:00 ET

Room: 710B

Session Available As: On-Demand

Co-Author(s)

Sarina Levy-Mendelovich, MD

Senior Pediatric Hemato-oncologist
The National Hemophilia Center, and Amalia Biron Research Institute of Thrombosis and Hemostasis, Sheba Medical Center, Ramat Gan, Israel
Tel Aviv, HaMerkaz, Israel

Co-Author(s)

NA

Nitzan Atia

Researcher
Sheba Medical Center
Tel Hashomer, Tel Aviv, Israel
IB

Ivan Budnik

MD Phd
University of IOWA
Iowa city, Iowa, United States

Presenting Author(s)

Assaf Barg, MD

Pediatric Hematologist
The National Hemophilia Center, and Amalia Biron Research Institute of Thrombosis and Hemostasis, Sheba Medical Center, Ramat Gan, Israel
Tel Aviv, HaMerkaz, Israel

Co-Author(s)

EA

Einat Avishai

Research Assistant, Molecular Biology Unit, Coagulation Laboratory, National Hemophilia Center and T
Tel Aviv University
Tel Aviv, HaMerkaz, Israel
RD

Rima Dardik

Head, Molecular Biology Unit, Coagulation Laboratory, National Hemophilia Center and Thrombosis Unit
Tel Aviv University
Tel Aviv, HaMerkaz, Israel
Omri Cohen, MD

Senior physician
Sheba medical center, Tel Aviv University
Holon, HaMerkaz, Israel
TB

Tami Brutman-Barazani

Researcher
Sheba Medical Center
Tel Hashomer, Tel Aviv, Israel
Tami Livnat, Prof. (she/her/hers)

Head - Basic Research Laboratory, Amalia Biron Research Institute of Thrombosis and Hemostasis, Sheb
Tel Aviv University
Tel Aviv, Tel Aviv, Israel
Gili Kenet, MD

Director
The National Hemophilia Center, and Amalia Biron Research Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer, Tel Aviv University, Tel Aviv, Israel
Yehud-Monosson, HaMerkaz, Israel

Background: Using Emicizumab in lieu of Immune tolerance induction (ITI) for patients with hemophilia A (HA) and FVIII inhibitors has been well described. However, some decisions regarding ITI initiation, regimen and preservation of tolerance remain to be elucidated.

Aims: To study the course of FVIII inhibitor in HA patients with a history of FVIII inhibitors, receiving Emicizumab prophylaxis.

Methods: Following informed consent, HA patients with current or past inhibitor initiating Emicizumab therapy were followed. Plasma samples were obtained every 3-6 months or following FVIII exposure day (ED) for chromogenic BU assays. Patients documented annual bleeding rate (ABR) and any FVIII ED.

Results: Fifty-one patients met inclusion criteria, whose data are sown in table 1. For inhibitor analyzes see Figure 1. Among all patients followed for a median of 3.3 years, ABR decreased. 22/51 patients experienced 31 breakthrough bleeding episodes. Among our failed ITI patients, in 5/15 inhibitor level transiently increased following FVIII exposures. In patients who deferred ITI, 8/21 patients were exposed to FVIII (1-2 ED) among whom only 1/8 increased inhibitor levels after head trauma (1ED). In patients that underwent successful ITI ,8/15 patients were exposed to a total of 13 ED (1-2 ED each) for traumatic breakthrough bleeds. In all these patients, inhibitor levels remained zero, preserving their successful tolerance.

Conclusion(s): Our study shows that in a longitudinally followed cohort of HA patients with FVIII inhibitor, occasional exposure to FVIII may induce a transient anamnestic response. Non the less, in patients who underwent successful ITI neither permanent inhibitor increased nor FVIII inhibitor recurrence were noted.

Learning Objectives:

Describe data published regarding use of emicizumab in lieu of ITI.
Describe our center's experience with patients treated with emicizumab following ITI.
Compare the natural course of FVIII inhibitors in hemophilia A patients treated with emicizumab between patients that underwent ITI and those that did not.