Effect of the tyrosine kinase inhibitor nilotinib in patients with hypereosinophilic syndrome/chronic eosinophilic leukemia: analysis of the phase 2, open-label, single-arm A2101 study.

purposeHypereosinophilic syndrome (HES) and chronic eosinophilic leukemia (CEL) are characterized by sustained overproduction of eosinophils and organ dysfunction. CEL involves the presence of clonal genetic markers, such as a fusion of FIP1-like 1 protein and platelet-derived growth factor receptor α (FIP1L1-PDGFRα, or F/P) or PDGFRα-activating mutations.

methodsSixteen patients with HES/CEL were enrolled in the phase 2 nilotinib registration trial (NCT00109707) and treated with nilotinib 400 mg twice daily. The median duration of treatment was 95 days (range 3-1,079).

resultsTwelve patients had HES: 1 achieved a complete hematologic response (CHR), 3 achieved stable disease, 3 had progressive disease, and 5 were not evaluable for response. Four patients had CEL: 2 with the F/P fusion and 2 with PDGFRα-activating mutations. Both patients with an F/P fusion achieved a CHR; 1 also achieved a complete molecular response (CMR). Of the 2 patients with PDGFRα-activating mutations, 1 had stable disease and the other achieved CMR. At 24 months, overall survival in the HES group was 75.0 % (95 % CI 50.5-100.0) and no patients in the CEL group died. Median survival was not yet reached after a median follow-up of 32 months. The most common grade 3/4 hematologic laboratory abnormalities were lymphocytopenia (31.3 %) and neutropenia (25.0 %). The most common drug-related nonhematologic grade 3/4 adverse event was pruritus, which occurred in 2 patients (12.5 %).

conclusionsNilotinib 400 mg twice daily was effective in some patients with HES/CEL regardless of F/P mutation status, and the safety profile was consistent with other nilotinib studies.