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.
Original language | English (US) |
---|---|
Pages (from-to) | 1985-1993 |
Number of pages | 9 |
Journal | Journal of Cancer Research and Clinical Oncology |
Volume | 139 |
Issue number | 12 |
DOIs | |
State | Published - Dec 2013 |
Funding
Conflict of interest AH received research funding from Novartis Pharmaceuticals Corporation. PDlC received research funding from Novartis and honoraria as a speaker from Novartis, Bristol-Myers Squibb (BMS), Pfizer, and ARIAD Pharmaceuticals. HMK received research funding from Novartis Pharmaceuticals Corporation, Pfizer, ARIAD Pharmaceuticals, and BMS. MB acted as a consultant, received honoraria and attended a speakers’ bureau for Novartis Pharmaceuticals Corporation, BMS, and Pfizer. PE has no financial conflicts to disclose. AR acted as a consultant and received honoraria from Novartis Pharmaceuticals Corporation. TM and XF are employees of Novartis Pharmaceuticals Corporation. SN is an employee and stockholder of Novartis Pharmaceuticals Corporation. FJG acted as a consultant and received research funding from Novartis Pharmaceuticals Corporation.
Keywords
- Chronic eosinophilic leukemia
- Hypereosinophilic syndrome
- Nilotinib
ASJC Scopus subject areas
- Oncology
- Cancer Research