Background: Corticosteroids and imatinib are the first line treatment in hypereosinophilic syndromes (HES) according FIP1L1-PDGFRA (F/P) positivity. In HES unrelated to F/P, second line available treatment are historically interferon alpha (IFN-α) and hydroxyurea, while anti-interleukin-5 antibodies are currently investigated. Data concerning efficacy of IFN-αin HES are limited to small case series and one large international study with a short-term follow-up.
Methods: We performed a multicenter, retrospective, descriptive study to evaluate the efficacy and safety of IFN-αin F/P-negative HES patients. Complete hematologic responses (CHR : eosinophils < 0,5 G/L) and partial hematologic responses (PHR: eosinophils between 0,5 to 1,5 G/L or a decrease of more than 50%), as well as tolerance and corticosteroid sparing-effect were analyzed at 1, 3, 6 and 12 months.
Results: Twenty-nine patients (9 women, with a mean [+/-SD]age at diagnosis of 38 [+/-13]years were included. Fifteen patients (52%) had idiopathic HES, 10 (34%) had a lymphocytic HES, and 4 (14%) had a clonal HES. The most common clinical manifestations were cutaneous (69%) and gastrointestinal involvement (31%). IFN-αwas used in pegylated form in 16 patients at an average dose of 113 [+/-45 μg]/week and in non-pegylated form in 13 patients at an average dose of 12 [+/-9]MIU / week. At one month, a CHR or PHR was observed in 24 patients (83%), including 16 in CHR. At 1 year, 16 patients were still treated with IFN-α, (9 in CHR and 7 in PHR). Treatment with IFN-αwas associated with a significant decrease in the mean daily prednisone dose from 20 [+/-16]mg/day at inclusion to 11 [+/-6]mg/day at 6 months and at 9 [+/-9]mg/j at 1 year. After a median of 15 months (range 1 to 161 months), 21 patients (72%) discontinued IFN-αmainly due to adverse events (27%) or loss of efficacy (31%). At the end of the follow-up, 8 patients were still on IFN-αwith a median duration of treatment of 21.5 months (3 to 161 months), including 6 in CHR and 2 in RHP. In these 8 patients, pegylated IFN-αwas used at the median maintenance dose of 50 μg/week with maintenance of a corticosteroid sparing-effect (median daily prednisone dose at 5.5 mg/day).
Conclusions: IFN-αappears to be an effective treatment for corticosteroid-resistant or corticosteroid-dependent F/P-negative HES. Its effectiveness can be maintained over long term and at low dose in nearly a quarter of patients, with good tolerance. However, a loss of efficacy or adverse effects justify discontinuation of IFN-αin the majority of cases, underlying the need of alternative therapies
No relevant conflicts of interest to declare.
Interferon-Alpha is an off-label drug used in hypereosinophilic syndromes since more than 20 years.
Author notes
Asterisk with author names denotes non-ASH members.
