Study Evaluates Cross-intolerance Among TKIs for CP-CML
Dasatinib may be an appropriate treatment option for patients with chronic myeloid leukemia in chronic-phase who are intolerant to imatinib.
Dasatinib may be an appropriate treatment option for patients with chronic myeloid leukemia in chronic-phase (CP-CML) who are intolerant to imatinib, with cross-intolerance leading to discontinuation in only a small proportion of patients, a study published in the journal Clinical Lymphoma, Myeloma & Leukemia has shown.1
Although BCR-ABL inhibitors like imatinib have improved the prognosis of patients with CML, first-line imatinib is often discontinued due to resistance or intolerance. Dasatinib is a common second-line option; however, researchers sought to determine whether cross-intolerance is present between imatinib and dasatinib, a second-generation BCR-ABL inhibitor.
For the study, researchers retrospectively analyzed data from 271 imatinib-intolerant patients who participated in phase 2 or 3 studies.
Results showed that 17% of the 271 patients experienced cross-intolerance to dasatinib based on recurrence of grade 3 or 4 adverse events.
Researchers found that of the 228 patients who discontinued imatinib due to nonhematologic intolerance, 4% experienced the same severe nonhematologic adverse events with dasatinib. Two percent of those patient discontinued dasatinib treatment due to cross-intolerance.
Further, 86% of the 43 patients who discontinued imatinib therapy because of hematologic toxicity had recurrence of grade 3 or 4 hematologic adverse events with dasatinib, with 19% discontinuing dasatinib due to cross-intolerance.
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The study also demonstrated that estimated 2-year progression-free survival and overall survival after a median treatment duration of 22 months were higher in patients with nonhematologic intolerance to imatinib who switched to dasatinib compared with those with hematologic intolerance who switched.
- Khoury HJ, Goldberg SL, Mauro MJ, et al. Cross-intolerance with dasatinib among imatinib-intolerant patients with chronic-phase chronic myeloid leukemia [published online ahead of print March 29, 2016]. Clin Lymphoma Myeloma Leuk. doi: 10.1016/j.clml.2016.03.004.