In general, acquired pan-inhibitors represent a rare and difficult to treat problem, with serious consequences for the patient. Most experience is in the setting of hemophilia. The optimal therapeutic strategy for inhibitor eradication is not yet been defined and is based on immunosupression. The immunosuppressive regimen most
have included corticosteroid therapy alone or in combination with cyclophosphamide.
The response rate reported in the literature is variable: corticosteroids 42-70%, corticosteroids + cyclophosphamide 50-84%. A retrospective
registry in the UK showed no difference in inhibitor eradication or disease-free survival between these two therapies. Recent reports have shown promising results
with Rituxan. A recent literature review based on uncontrolled studies or case reports suggests remission obtained in 79% of patients (N=43)
and no reported cases of opportunistic infections. At present this drug is recommended as second line therapy if cyclophosphamide and/or corticosteroids have failed or were contraindicated.
Recently, a combination of two immunosupressives was reported as a case series of low-dose rituximab plus alemtuzumab in patients with steroid-refractory autoimmune hemolytic anemia and immune thrombocytopenic purpura. There were 22 patients and 19 were assessable. Treatment with 10 mg of alemtuzumab subcutaneously on days 1 to 3, plus 100 mg of rituximab intravenously weekly in 4 doses, was administered. The overall response rate was 100%, with complete response in 58%. The median response duration was 46 weeks (range, 16-89 weeks). Median follow-up was 70 weeks (range, 37-104 weeks). Most toxicity was grade 1 fever related to the first dose. Six patients developed infections. The authros concluded that the combination of rituximab and alemtuzumab is feasible and has an acceptable safety profile and remarkable clinical activity in this group of patients.
Huth-Kuhne A, Baudo F, Collins P, Ingerslev J, Kessler CM, Levesque H, et al. International recommendations on the diagnosis and treatment of patients with acquired hemophilia A. Haematologica 2009;94:566-75.
David Gómez-Almaguer, et al, Low-dose rituximab and alemtuzumab combination therapy for patients with steroid-refractory autoimmune cytopenias Blood 2010 116:4783-4785