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

• Published in: Journal of cancer research and clinical oncology Vol. 139; no. 12; pp. 1985 - 1993
• Main Authors: Hochhaus, Andreas, le Coutre, Philipp D., Kantarjian, Hagop M., Baccarani, Michele, Erben, Philipp, Reiter, Andreas, McCulloch, Tracey, Fan, Xiaolin, Novick, Steven, Giles, Francis J.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.12.2013; Springer; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic agents; Biological and medical sciences; Cancer Research; Chronic Disease; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Hematologic and hematopoietic diseases; Hematology; Humans; Hypereosinophilic Syndrome - drug therapy; Hypereosinophilic Syndrome - mortality; Hypereosinophilic Syndrome - pathology; Inhibitor drugs; Internal Medicine; Kinases; Leukemia; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Oncology; Original Paper; Other diseases. Hematologic involvement in other diseases; Pharmacology. Drug treatments; Protein Kinase Inhibitors - administration & dosage; Pyrimidines - administration & dosage; Side effects; Treatment Outcome; Nilotinib; Chronic eosinophilic leukemia; Hypereosinophilic syndrome; Human; Eosinophilic leukemia; Enzyme; Tyrosine kinase inhibitor; Toxicity; Transferases; Granulocyte; Enzyme inhibitor; Malignant hemopathy; Myeloproliferative syndrome; Chronic; Treatment; Phase II trial; Protein-tyrosine kinase; Cancer
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-013-1529-7

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.