PB1290 - Successful very low dose immune tolerance induction with albutrepenonacog alfa in a severe hemophilia B child with anaphylactic reaction to factor IX

Tuesday, June 27, 2023

18:30 – 19:30 ET

Room: Exhibition

Co-Author(s)

Ihosvany Fernández-Bello, PhD (he/him/his)

Postdoctoral Researcher
Hemostasis and Thrombosis Unit, Regional University Hospital of Málaga, IBIMA, Málaga, Spain.
Málaga, Andalucia, Spain

Presenting Author(s)

Francisco José López Jaime, MD

Hematologist
Hemostasis and Thrombosis Unit, Regional University Hospital of Málaga, IBIMA, Málaga, Spain.
Málaga, Andalucia, Spain

Co-Author(s)

AM

Adrián Montaño, PhD (he/him/his)

Postdoctoral researcher
Hemostasis and Thrombosis Unit, Regional University Hospital of Málaga / University of Salamanca
Málaga, Andalucia, Spain

Co-Author(s)

RP

Rosario Prieto Bonilla

Hematologist
Hematology Service, Hospital Materno-Infantil de Málaga, Málaga, Spain.
Málaga, Andalucia, Spain
DB

Daniel Bardán Rebollar

Hematologist
Hematology Service, Hospital Materno-Infantil de Málaga, Málaga, Spain.
Málaga, Andalucia, Spain
�P

Ángeles Palomo Bravo

Hematologist
Hematology Service, Hospital Materno-Infantil de Málaga, Málaga, Spain.
Malaga, Andalucia, Spain

Background: The development of inhibitors is the most serious complication in hemophilia patients. Immune tolerance induction (ITI) is the only treatment option to eradicate it. However, ITI is challenging in hemophilia B (HB) due to the limited experience and the associated development of allergic/anaphylactic reactions and nephrotic syndrome.

Aims: We present the case of a child with severe HB (SHB) with inhibitor who was subjected to a less aggressive ITI strategy given his young age and the strong anaphylactic response to a standard recombinant factor IX (rFIX).

Methods: A 10-month-old male, diagnosed with SHB, started treatment on-demand with rFIX.

Results: After 6 exposure days, the patient presented a strong anaphylactic reaction and FIX inhibitor titer of 3.6 BU/mL. Treatment with rFIX was switched to recombinant activated FVII (rFVIIa) on demand. Once inhibitor levels reached 0.4 BU/mL, prophylaxis was resumed with an extended half-life rFIX concentrate (albutrepenonacog alfa [rFIX-FP]) at increasing doses of 20 IU/kg, 40 IU/kg and 50 IU/kg along 3 consecutive weeks. After the third dose, inhibitor titer of 12.8 BU/mL was detected, and rFIX-FP suspended until reaching inhibitor titer of 0.3 BU/mL when we decided to start ITI with very low dose and stepped exposition (desensitization strategy starting with 5 IU/kg/week x 10 doses) of rFIX-FP combined with rFVIIa prophylaxis. After three months of ITI, the patient showed no inhibitor until the present day (15 months of follow-up). Patient is currently on prophylaxis with rFIX-FP (35 IU/kg/week) and trough FIX levels of 7.1%.

Conclusion(s): The desensitization strategy using rFIX-FP might be a plausible option for inhibitor eradication in SHB, especially in those at high risk of developing anaphylactic reactions and/or inhibitor to FIX. This strategy might increase the efficacy of ITI, reduce the number of venipunctures and the economic cost of ITI in SHB.