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

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 x 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.