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

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.