Hanna J Khoury1, Stuart L Goldberg2, Michael J Mauro3, Richard M Stone4, Michael W Deininger5, M Brigid Bradley-Garelik6, Hesham Mohamed6, François Guilhot7. 1. Division of Hematology, Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA. Electronic address: hkhoury@emory.edu. 2. John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ. 3. Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY. 4. Dana-Farber Cancer Institute, Boston, MA. 5. Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT. 6. Bristol-Myers Squibb, Princeton, NJ. 7. Department of Oncology, Hematology, and Cell Therapy, Centre Hospitalier Universitaire de Poitiers, Clinical Investigation Center, Inserm 0802, Poitiers, France.
Abstract
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 nonhematologic intolerance, 10 (4%) experienced the same severe nonhematologic 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.
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 CMLimatinib-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 nonhematologic intolerance, 10 (4%) experienced the same severe nonhematologic 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.