Imatinib at Weekly Dosage May Induce and Maintain Haematologic and Molecular Remission in Chronic Eosinophilic Leukemia Harbouring FIP1L1-PDGFRA Fusion Gene- An Extended Follow-up Study.

Background. A small proportion of patients with hypereosinophilic syndrome (HES) demonstrate the presence of an interstitial deletion in chromosome 4 leading to the creation of the imatinib-responsive fusion gene- FIP1L1-PDGFRA (F/P). Recently, we showed that a single weekly dose of imatinib is sufficient to induce and maintain remission of chronic eosinophilic leukemia (CEL) with detectable F/P transcript. Here, we present data from 12 patients CEL and HES, 11 of which were F/P positive, who achieved a rapid complete haematologic remission (CHR) with daily imatinib treatment and remission was then maintained with a weekly imatinib schedule.

Design and methods. Twelve patients, 11 out of 12 with detectable F/P were treated with imatinib at the initial doses varies between 100–400mg. There were 10 male and 2 female with a median age of 57 years (19–80). Median time to start imatinib was 23 months (1–204 months). The imatinib dose was de-escalated while patients remained in haematologic remission. As a response maintenance, once weekly imatinib was established in all cases.

Results. All studied patients achieved a complete haematologic remission (CHR) and 100% of cases with detectable F/P fusion gene before imatinib, demonstrated a molecular remission determined by reverse transcriptase polymerase chain reaction (RT-PCR) analysis. The breakpoints occured within exon 12 of PDGFRA whereas breakpoints dispersed across the FIP1L1 locus occuring between exons 10 and 13. Median time to achieve CHR was 13 days (4–90), and median time to molecular remission was 9 months (4–24). As a remission maintenance, imatinib doses were set at 100mg weekly in 9 pts and 200mg weekly in 3. With a median follow-up of 21 months (8–49 months) all pts remain in CHR. The FIP1L1-PDGFRA is undetectable in 11 patients by RT-PCR.

Conclusions. Imatinib at weekly dosage may induce and maintain remission in patient with CEL expressing F/P fusion gene. This strategy appears to be safe and cost savings.