Imatinib in the treatment of chronic myeloid leukemia: current perspectives on optimal dose

摘要

Imatinib was the first tyrosine kinase inhibitor (TKI), successfully used in a clinical setting. It inhibits activity of BCR-ABL1 oncogenic tyrosine kinase which is crucial in the pathogenesis of chronic myeloid leukemia (CML). The safety and efficacy of imatinib dose 400 mg daily was established in several clinical studies. Nevertheless, imatinib dose escalation (≥600 mg daily) has been widely explored as an option to improve clinical outcomes. Results of the meta-analysis comparing frontline therapy with imatinib 400 mg daily vs high dose (HD, ≥600 mg daily) in patients with chronic phase CML (CML-CP) showed that the rate of complete cytogenetic response as well as major molecular response (MMR) at 12 months was significantly higher in HD imatinib group. However, HD imatinib does not improve overall survival and progression-free survival. Thus, the routine use of HD imatinib as frontline treatment for CML-CP is not recommended. In patients with CML-CP resistant to standard dose, HD imatinib does not significantly improve patient outcomes without a prior cytogenetic response. Therefore, in second-line therapy, the current CML-CP treatment guidelines do not recommend imatinib dose escalation but the use of second-or third-generation TKIs. In the therapy of TKI-na?ve patients with accelerated or blastic phase of CML, HD imatinib (400 mg twice daily) is one of the recommended standards. In case of disease progression while on imatinib, second- or third-generation TKIs should be administered.