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.

Abstract

PURPOSE:

Hypereosinophilic 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.

METHODS:

Sixteen 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).

RESULTS:

Twelve 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 %).

CONCLUSIONS:

Nilotinib 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.

• Authors: Andreas Hochhaus, Philipp D le Coutre, Hagop M Kantarjian, Michele Baccarani, Philipp Erben, Andreas Reiter, Tracey McCulloch, Xiaolin Fan, Steven Novick, Francis J Giles
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 139 Issue 12 Pg. 1985-93 (Dec 2013) ISSN: 1432-1335 [Electronic] Germany
• PMID: 24057647 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)

Chemical References

• Protein Kinase Inhibitors
• Pyrimidines
• nilotinib

Topics

• Adult
• Aged
• Aged, 80 and over
• Chronic Disease
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Female
• Humans
• Hypereosinophilic Syndrome (drug therapy, mortality, pathology)
• Male
• Middle Aged
• Protein Kinase Inhibitors (administration & dosage)
• Pyrimidines (administration & dosage)
• Treatment Outcome