DISCUSSION
Like BCR ABL-positive CML in sustained CMR, for which recommendations have been established, Imatinib discontinuation in FIP1L1-PDGFRA-positive HES in sustained CMR is under evaluation. Because of the limited number of cases of SHE, there is little data on treatment discontinuation, and in the literature only a few studies report experience with treatment-free remission.
Our case represents a FIP1L1-PDGFRA-positive HES, treated with Imatinib, who achieved CHR and CMR, and for whom Imatinib was stopped after 6 years (77 months) of treatment. Currently, 9 months after stopping treatment, the patient maintains in CHR and CMR.
Epidemiologically, there is a clear male predominance in clonal HES. Rohmer et al. found a sex ratio of 18/1 and Legrand et al. a sex ratio of 43/1 in their cohorts. The median age was 49 ± 12 years for Rohmer and 41 years for Legrand. [1, 2] Our case was a 58-years-old patient at diagnosis. He presented with skin and lung involvement of hypereosinophilia, which are frequent manifestations of the disease. [1, 3]
After 77 months of treatment, the patient was advised to stop Imatinib. The literature reports several cases of safe discontinuation of Imatinib with maintenance of CMR and CHR without treatment. Relapses also occur, but to date no factors that predict the risk of relapse have been found. Indeed, it would appear that the length of treatment before stopping Imatinib does not influence the risk of relapse. Our patient was treated for 77 months (6 years) before stopping Imatinib. In Helbig et al study [4], the median treatment duration was 79.2 months, the relapse rate was 42.8% at 6 months and the relapse-free survival at 12 months was 57%. In Klion et al study [5], duration of treatment was 25.5 months, the relapses occured within 6 months of stopping. In Legrand et al study [2], the median treatment duration was 30.2 months, fifty-five percent of relapses were observed after a treatment free duration of 1 to 27 months, relapse-free survival was 61% at 12 months and 42% at 24 months. Qu et al. [3] report 50% of relapse within 2 to 48 months after a median of 17.5 months of treatment. Therefore, duration of Imatinib treatment does not appear to be related to relapse. [3]
The dose of Imatinib maintenance therapy also does not affect the risk of relapse. In these different studies, the dose varied from 200mg per day to 100mg per day or 100mg three times a week or 100mg a week and even 50mg a week. In our case, the maintenance dose was 100mg/day.
On the other hand, the time between the onset of HES and the initiation of Imatinib would decrease the risk of relapse. Rohmer et al. [1] found that a rapid relapse was associated with a long delay of initiation of therapy. In their cohort, the median time to treatment initiation was 11 months (3-28), leading to a relapse-free survival of 57% at 58 months.
In our case, the time between starting Imatinib and discovering of hypereosinophilia was 6 months. Currently, at 9 months after withdrawal of Imatinib, the patient remains in CMR. No signs of TKI withdrawal syndrome were observed in our patient.
The duration of CMR before withdrawal Imatinib would also have no impact on relapse. However, according to Qu et al [3], stopping treatment at CMR and not at CHR would decrease the risk of relapse.
At relapse, in Metzgeroth et al. study [6], 3/4 of patients achieved a second CMR after restarting Imatinib at a dose of 100mg daily. In Rohmer et al. study [1], CHR was achieved within 1 month and CMR within 12 months after restart in 17/20 patients. Qu et al [3] were more prudent, because in their study 50% of patients relapsed after discontinuing Imatinib, and therefore they recommended not to withdrawal the treatment.