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. 2016 Jun;71(6):803-10.
doi: 10.1111/all.12843. Epub 2016 Mar 2.

Clinical features predict responsiveness to imatinib in platelet-derived growth factor receptor-alpha-negative hypereosinophilic syndrome

P Khoury  1 , R Desmond  2   3 , A Pabon  1 , N Holland-Thomas  4 , J M Ware  1 , D C Arthur  5 , R Kurlander  6 , M P Fay  7 , I Maric  6 , A D Klion  1
Affiliations

Clinical features predict responsiveness to imatinib in platelet-derived growth factor receptor-alpha-negative hypereosinophilic syndrome

P Khoury et al. Allergy. 2016 Jun.

Abstract

Background: With the exception of the presence of the FIP1L1-PDGFRA fusion gene, little is known about predictors of imatinib response in clinically-defined hypereosinophilic syndrome (HES).

Methods: Subjects with FIP1L1-PDGFRA-myeloid neoplasm (FP; n =12), PDGFRA-negative HES with ≥4 criteria suggestive of a myeloid neoplasm (MHES; n =10), or steroid-refractory PDGFRA-negative HES with <4 myeloid criteria (SR; n = 5) were enrolled in a prospective study of imatinib therapy (NCT00044304: registered at clinicaltrials.gov). The primary outcome was an eosinophil count <1.5 × 109/L at one month and improvement of clinical symptoms. Clinical, molecular, and bone marrow responses to imatinib were assessed. A retrospective cohort of 18 subjects with clinically-defined HES who received imatinib (300-400 mg daily ≥ 1 month) were classified according to the criteria used in the prospective study.

Results: Overall, imatinib response rates were 100% in the FP group (n = 16), 54% in the MHES group (n = 13) and 0% in the SR group (n = 16). The presence of ≥ 4 myeloid features was the sole predictor of response. After ≥ 18 months in complete remission, imatinib was tapered and discontinued in 8 FP and 1 MHES subjects. Seven subjects (6 FP, 1 MHES) remain in remission off therapy for a median of 29 months (range 14-36).

Conclusions: Clinical features of MHES predict imatinib response in PDGFRA-negative HES.

Trial registration: ClinicalTrials.gov NCT00044304 NCT00001406.

Keywords: PDGFRA-negative; eosinophilia; hypereosinophilic syndrome; imatinib; myeloid neoplasm.

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Conflict of interest statement

Conflicts of interest

No conflicts of interest are reported for any of the authors.

Figures

Figure 1
Figure 1
Imatinib response rates differ between corticosteroid nonresponder (SR), PDGFRA-associated (FP), and myeloid (MHES) groups. Response rates are shown separately for the prospective (A) and retrospective (B) cohorts. Peripheral eosinophil counts pre- and 1 month post-imatinib are shown for the prospective and retrospective cohorts combined (C-E). FP—FIP1L1-PDGFRA-associated myeloid neoplasm, MO—month, MHES—PDGFRA-negative, myeloid HES, SR —PDGFRA-negative, nonmyeloid, corticosteroid nonresponder.
Figure 2
Figure 2
Bone marrow cellularity, eosinophilia, and fibrosis were significantly improved in FP subjects but not in MHES or SR subjects in the prospective cohort. Bone marrow percent cellularity, percent eosinophilia, and fibrosis grade before and one month after initiation of imatinib therapy are shown for subjects with PDGFRA-associated disease (FP) (n = 11), PDGFRA-negative MHES who were imatinib-responsive (MHES-R) (n = 5) or imatinib-unresponsive (MHES-NR) (n = 3), and PDGFRA-negative, corticosteroid-resistant HES without myeloid features (SR) (n = 4). *P < 0.05 or **P < 0.01 as compared to pre, Wilcoxon matched pairs signed rank test.
Figure 3
Figure 3
Clinical features suggestive of a myeloid neoplasm are associated with imatinib responsiveness in PDGFRA-negative patients. The response to imatinib (responders—black bars, nonresponder—gray bars) is shown as a function of the number of features suggestive of a myeloid neoplasm in the PDGFRA-negative subjects in the combined prospective and retrospective cohorts.
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References

    1. Baccarani M, Cilloni D, Rondoni M, Ottaviani E, Messa F, Merante S et al. The efficacy of imatinib mesylate in patients with FIP1L1-PDGFRalpha-positive hypere-osinophilic syndrome. Results of a multicenter prospective study. Haematologica 2007;92:1173–1179. - PubMed
    1. Cools J, DeAngelo DJ, Gotlib J, Stover EH, Legare RD, Cortes J et al. A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med 2003;348:1201–1214. - PubMed
    1. Helbig G, Hus M, Halasz M, Dudzinski M, Wieclawek A, Stachowicz M et al. Imatinib mesylate may induce long-term clinical response in FIP1L1-PDGFRalpha-negative hypereosinophilic syndrome. Med Oncol 2012;29:1073–1076. - PubMed
    1. Helbig G, Moskwa A, Hus M, Piszcz J, Swiderska A, Urbanowicz A et al. Durable remission after treatment with very low doses of imatinib for FIP1L1-PDGFRalpha-positive chronic eosinophilic leukaemia. Cancer Chemother Pharmacol 2011;67:967–969. - PMC - PubMed
    1. Klion AD, Robyn J, Akin C, Noel P, Brown M, Law M et al. Molecular remission and reversal of myelofibrosis in response to imatinib mesylate treatment in patients with the myeloproliferative variant of hypere-osinophilic syndrome. Blood 2004; 103:473–478. - PubMed

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