| Abstract: |
Some patients with chronic myeloid leukemia (CML) are intolerant to first-line imatinib treatment. Our retrospective data analysis of 271 CML imatinib-intolerant patients from phase II and III studies examined the extent of cross-intolerance between imatinib and dasatinib. Our results have confirmed the clinical safety and efficacy of dasatinib in imatinib-intolerant CML patients, suggesting that dasatinib could be a suitable treatment choice for this population. Background: BCR-ABL inhibitors have improved the prognosis of patients with chronic myeloid leukemia (CML). However, imatinib, the first approved BCR-ABL inhibitor, must be discontinued in many patients because of resistance or intolerance. Patients and Methods: The present retrospective, pooled analysis of phase II and III data explored the extent of cross-intolerance between imatinib and dasatinib, a second-generation BCR-ABL inhibitor, in 271 CML imatinib-intolerant patients. Results: Overall, 47 patients (17%) had cross-intolerance to dasatinib, determined by recurrence of grade 3 or 4 adverse events (AEs). Of the 228 patients who discontinued imatinib because of non-hematologic intolerance, 10 (4%) experienced the same severe non-hematologic AEs with dasatinib, with 4 of these patients (2%) discontinuing dasatinib because of cross-intolerance. Of the 43 patients who discontinued imatinib because of hematologic intolerance, 37 (86%) experienced a recurrence of grade 3 or 4 hematologic AEs with dasatinib, with 8 patients (19%) discontinuing dasatinib because of cross-intolerance. Of the 43 patients taking dasatinib at the optimized dose of 100 mg/d, 1 (2%) discontinued therapy because of recurrence of nonhematologic AEs and 3 (7%) because of recurrence of hematologic AEs. With a median treatment duration of 22 months, the estimated rates of progression-free survival and overall survival at 2 years were greater for patients with nonhematologic versus hematologic intolerance to imatinib who switched to dasatinib (progression-free survival, 94% vs. 68%, respectively; overall survival, 98% vs. 88%, respectively). Conclusion: Dasatinib could be an appropriate treatment option for imatinib-intolerant patients with CML, with cross-intolerance resulting in discontinuation in a few patients. (C) 2016 Elsevier Inc. All rights reserved. |
