Phase II trial of imatinib mesylate in patients with PDGFRA/B-negative hypereosinophilic syndrome.

Autor: Kim DH; Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.; Department of Translational Medicine, Seoul National University College of Medicine, Seoul, Korea., Kim S; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea., Park S; Department of Internal Medicine, Inje University Haeundae Paik Hospital, Busan, Korea., Byun JM; Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.; Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea., Hong J; Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.; Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.; Cancer for Medical Innovation, Seoul National University Hospital, Seoul, Korea., Shin DY; Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.; Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.; Cancer for Medical Innovation, Seoul National University Hospital, Seoul, Korea., Kim I; Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea., Bang SM; Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea., Lee JO; Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea., Lee JY; Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea., Kim SA; Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea., Kim KH; Department of Internal Medicine, Seoul National University Boramae Hospital, Seoul, Korea., Chung YJ; Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Korea.; Integrated Research Center for Genome Polymorphism, Precision Medicine Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea., Jung SH; Integrated Research Center for Genome Polymorphism, Precision Medicine Research Center, College of Medicine, The Catholic University of Korea, Seoul, Korea.; Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul, Korea., Koh Y; Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.; Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.; Cancer for Medical Innovation, Seoul National University Hospital, Seoul, Korea., Yoon SS; Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.; Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.; Cancer for Medical Innovation, Seoul National University Hospital, Seoul, Korea.
Jazyk: angličtina
Zdroj: British journal of haematology [Br J Haematol] 2024 Oct 10. Date of Electronic Publication: 2024 Oct 10.
DOI: 10.1111/bjh.19828
Abstrakt: The role of imatinib in PDGFRA/B-negative hypereosinophilic syndromes (HES) is controversial because of the heterogeneity of HES and the scarcity of prospective studies. We conducted a phase II clinical trial to evaluate the efficacy of imatinib in PDGFRA/B-negative HES. Thirty-two patients were treated with imatinib (100-400 mg daily), and the molecular basis of their response was identified using whole-exome sequencing (WES) and whole-transcriptome sequencing (WTS). The haematological response rate was 46.9%, with a complete haematological response (CHR) rate of 18.8%. The median time to response was 1.5 months. Among the six patients who achieved CHR, five maintained it until the 24th cycle of imatinib and one lost response after 20 months. The median progression-free survival was 4.3 months. WES and WTS were conducted for 11 patients. The number of non-silent mutations did not differ between responders and non-responders. Nine differentially expressed genes, including SNORD15A, were downregulated in responders. STAT5B::RARA, PAK2::PIGX, and FIP1L1::CHIC2 fusions were identified in patients with sustained responses, and RNF130::BRAF and WNK1::KDM5A fusions were identified in non-responders. Imatinib, along with an appropriate biomarker, could be a promising option for PDGFRA/B-negative HES.
(© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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