Outcomes of low-dose immune tolerance induction with single-dose rituximab in severe hemophilia A: a single-center retrospective experience.

BACKGROUND

Low-dose immune tolerance induction (ITI) combined with standard-dose rituximab-based immunosuppression (LD-ITI + RTX-IS) is an effective strategy for factor VIII (FVIII) inhibitor eradication in severe hemophilia A with poor-risk prognostic factors for ITI, but optimal rituximab dosing remains undefined. Prolonged rituximab exposure increases adverse effects and financial burden.

AIM: To describe the outcomes and tolerability of LD-ITI combined with single-dose rituximab (LD-ITI + SD-RTX-IS) for FVIII inhibitor eradication in severe hemophilia A.

METHODS

A single-center retrospective cohort study was conducted in patients with severe hemophilia A and inhibitors who received LD-ITI + SD-RTX-IS. Treatment comprised FVIII (50 IU/kg every other day), rituximab (375 mg/m², single dose), and prednisone (1 mg/kg daily, tapering). Success was defined as inhibitor titer <0.6 BU/mL and FVIII recovery ≥66%.

RESULTS

A total of 16 patients (median age 17 years) were enrolled, comprising 8 adults and 8 children. Eleven of 16 patients (68.8%) achieved successful inhibitor eradication with a median time of 9.3 months (IQR: 2.8-15.2; range: 1.8-18.6); median FVIII recovery was 82%. The monthly bleeding rate decreased by 84.2% from pre-ITI (median: 4 episodes) to during ITI (median: 0.66 episodes), with a corresponding reduction in monthly joint bleeds from 3 to 0.46 episodes. At 24-month follow-up, no recurrence was documented. Adverse events were predominantly mild (rituximab-related infusion reactions, n=2; fever/pneumonia, n=4).

CONCLUSIONS

In this cohort, LD-ITI + SD-RTX-IS was associated with an inhibitor eradication rate consistent with prior LD-ITI + RTX-IS reports, using less rituximab. These preliminary findings warrant further prospective evaluation.