Imatinib mesylate for unmutated hypereosinophilic syndromes: Does it work?

  • Grzegorz Helbig
    Correspondence
    Department of Hematology and Bone Marrow Transplantation, Silesian Medical University, Dabrowski Street 25, 40-032 Katowice, Poland. Tel.: +48 3225 91310; fax: +48 3225 54985.
    Affiliations
    Department of Hematology and Bone Marrow Transplantation, School of Medicine in Katowice, Silesian Medical University, Katowice, Poland
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Published:March 08, 2016DOI:https://doi.org/10.1016/j.ejim.2016.02.024
      The high efficacy of tyrosine kinase inhibitor, imatinib mesylate (IM), is well-documented in patients with hypereosinophilic syndromes (HES) and detectable rearrangements of platelet-derived growth factor receptor α or β (PDGFRA/B) [
      • Gotlib J.
      World Health Organization-defined eosinophilic disorders. 2015 update on diagnosis, risk stratification and management.
      ]. Most of these IM responders were found to possess an interstitial deletion in chromosome 4q12 leading to constitutively active tyrosine kinase, FIP1L1-PDGFRA (F/P) [
      • Cools J.
      • De Angelo D.J.
      • Gotlib 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.
      ]. In contrast, the place of IM in the treatment of unmutated HES remains to be elucidated. Of note is, that IM was found to be ineffective in most HES patients with unknown or negative PDGFRA rearrangement. Among 18 treated patients, 1 complete and 2 partial responses were achieved. Starting IM dose was 100 mg daily for 4 weeks and the dose could be escalated to 400 mg daily if there was no response or disease progression. IM was used as frontline therapy in 7 patients [
      • Jain N.
      • Cortes J.
      • Quintas-Cardama A.
      • et al.
      Imatinib has limited therapeutic activity for hypereosinophilic syndrome patients with unknown or negative PDGFR alpha mutation status.
      ]. Only a few unmutated HES patients responded to standard IM doses in two large prospective studies, but response duration remained short in at least some of the treated cases [
      • Baccarani M.
      • Cilloni D.
      • Rondoni M.
      • et al.
      The efficacy of imatinib mesylate in patients with FIP1L1-PDGFRalpha-positive hypereosinophilic syndrome. Results of a multicenter prospective study.
      ,
      • Metzgeroth G.
      • Walc C.
      • Erben P.
      • et al.
      Safety and efficacy of imatinib in chronic eosinophilic laekaemia and hypereosinophilic syndrome—a phase II study.
      ].

      Keywords

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      References

        • Gotlib J.
        World Health Organization-defined eosinophilic disorders. 2015 update on diagnosis, risk stratification and management.
        Am J Hematol. 2015; 90: 1077-1089
        • Cools J.
        • De Angelo D.J.
        • Gotlib 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
        • Jain N.
        • Cortes J.
        • Quintas-Cardama A.
        • et al.
        Imatinib has limited therapeutic activity for hypereosinophilic syndrome patients with unknown or negative PDGFR alpha mutation status.
        Leuk Res. 2009; 33: 837-839
        • Baccarani M.
        • Cilloni D.
        • Rondoni M.
        • et al.
        The efficacy of imatinib mesylate in patients with FIP1L1-PDGFRalpha-positive hypereosinophilic syndrome. Results of a multicenter prospective study.
        Haematologica. 2007; 92: 1173-1179
        • Metzgeroth G.
        • Walc C.
        • Erben P.
        • et al.
        Safety and efficacy of imatinib in chronic eosinophilic laekaemia and hypereosinophilic syndrome—a phase II study.
        Br J Haematol. 2008; 143: 707-715
        • Helbig G.
        • Hus M.
        • Hałasz M.
        • et al.
        Imatinib mesylate may induce long-term clinical response in FIP1L1-PDGFRalpha-negative hypereosinophilic syndrome.
        Med Oncol. 2012; 29: 1073-1076
        • Helbig G.
        • Moskwa A.
        • Hus M.
        • et al.
        Durable remission after treatment with very low doses of imatinib for FIP1L1-PDGFRα-positive chronic eosinophilic leukemia.
        Cancer Chemother Pharmacol. 2011; 67: 967-969
        • Curtis C.E.
        • Grand F.H.
        • Musto P.
        • et al.
        Two novel imatinib-response PDGFRA fusion genes in chronic eosinophilic leukaemia.
        Br J Haematol. 2007; 138: 77-81
        • Intermesoli T.
        • Delaini F.
        • Acerboni S.
        • et al.
        A short low-dose imatinib trial allows rapid identification of responsive patients in hypereosinophilic syndromes.
        Br J Haematol. 2009; 147: 681-685
        • Khoury P.
        • Desmond R.
        • Pabon A.
        • et al.
        Clinical features predict response to imatinib in platelet derived growth factor receptor alpha-negative hypereosinophilic syndrome.
        Allergy. 2016; ([epub ahead of print]. Jan 21)https://doi.org/10.1111/all. 12843