Long-Term Remission Maintenance on Weekly Imatinib Dosage In Patients with FIP1L1-PDGFRA-Positive Chronic Eosinophilic Leukaemia

Abstract 4097

A small subset of patients with hypereosinophilic syndrome (HES) presents an interstitial deletion in chromosome 4q12, which leads to the expression of an imatinib -responsive fusion gene- called FIP1L1-PDGFRA (F/P). These patients have chronic eosinophilic leukemia (CEL). Here, we treated twenty five F/P-positive CEL patients (22 male, 2 female; median age of 50 years) with imatinib using initial daily doses ranging from 100 – 400 mg. At diagnosis a median peripheral blood eosinophilia and eosinophil marrow infiltration were 12×10⁹/L (range 2.5–40.8) and 39% (range 7–80), respectively. Splenomagaly was the most frequent clinical manifestation in this patient subgroup. All imatinib-treated patients achieved clinical and molecular response. A complete haematological remission (CHR) was demonstrated after median of 13 days (range 3–90) whereas molecular response (MR) was confirmed after median of 9 months (range 3–24). In a remission maintenance phase, imatinib doses were de-escalated and they were following: 100mg once weekly (n=11), 100mg twice weekly (n=6), 100mg daily (n=5), 200mg once weekly (n=2) and 400mg once weekly (n=1). Plasma imatinib level was measured 24 hours after the last drug intake in 7 patients treated in once weekly schedule and it remained extremely low, ranging between 44–167 ng/ml. Molecular studies performed at the same time points confirmed molecular remission. With a median follow-up of 40 months all patients remained in CHR and FIP1L1-PDGFRA expression was undetectable in all treated patients. These data indicate that even very low imatinib doses are highly effective in remission maintenance of patients with F/P-positive CEL.