Imatinib is effective in some PDGFRA/B‐negative hypereosinophilic syndromes: A step closer to unveiling underlying mechanisms

Hypereosinophilic syndromes (HES) comprise different clonal, reactive, or idiopathic disorders characterized by elevated eosinophil levels and subsequent organ damage. Kim et al. in a multicentre, single‐arm, prospective phase II study, treated 32 patients with PDGFRA/B‐negative HES with imatinib at the dose of 100–400 mg daily. Respective overall and complete haematological response rates were 46.9% and 18.8%, and the median time to response was 1.5 months. The molecular basis of responses was identified by using whole‐exome and whole‐transcriptome sequencing in 11 patients. STAT5B::RARA, PAK2::PIGX, and FIP1L1::CHIC2 fusions were identified in responders, whereas RNF130::BRAF and WNK1::KDM5A were identified in non‐responders. Imatinib could be a therapeutic option for some, possibly clonal, PDGFRA/B‐negative HES. Commentary on: Kim et al. Phase II trial of imatinib mesylate in patients with PDGFRA/B‐negative hypereosinophilic syndrome. Br J Haematol 2024; 205:2305‐2314.