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

• Published in: Allergy (Copenhagen) Vol. 71; no. 6; pp. 803 - 810
• Main Authors: Khoury, P., Desmond, R., Pabon, A., Holland‐Thomas, N., Ware, J. M., Arthur, D. C., Kurlander, R., Fay, M. P., Maric, I., Klion, A. D.
• Format: Journal Article
• Language: English
• Published: Denmark Blackwell Publishing Ltd 01.06.2016
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Allergies; Biomarkers; Blood platelets; Bone Marrow - pathology; Chemotherapy; eosinophilia; Eosinophils; Female; Follow-Up Studies; Humans; hypereosinophilic syndrome; Hypereosinophilic Syndrome - diagnosis; Hypereosinophilic Syndrome - drug therapy; Hypereosinophilic Syndrome - genetics; imatinib; Imatinib Mesylate - therapeutic use; Leukocyte Count; Male; Middle Aged; mRNA Cleavage and Polyadenylation Factors - genetics; myeloid neoplasm; PDGFRA‐negative; Phenotype; Prognosis; Protein Kinase Inhibitors - therapeutic use; Receptor, Platelet-Derived Growth Factor alpha - genetics; Rodents; Treatment Outcome; Tumors; Young Adult; eosinophilia; imatinib; PDGFRA-negative; hypereosinophilic syndrome; myeloid neoplasm
• ISSN: 0105-4538; 1398-9995; 1398-9995
• DOI: 10.1111/all.12843

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.