Cross-Intolerance With Dasatinib Among Imatinib-Intolerant Patients With Chronic Phase Chronic Myeloid Leukemia

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.