Imatinib: The First-Line CML Therapy

Abstract

Imatinib, the first TKI (tyrosine kinase inhibitor) of BCR-ABL1 introduced for the therapy of CML (chronic myelogenous leukemia), has profoundly changed the outcome perspectives of a disease previously fatal in the vast majority of the patients and which now shows an overall survival similar to that of a control population without leukemia. However, in addition to those who cannot tolerate the drug (approximately 10–15% of the total), 20–25% of the imatinib patients treated with the usual dosage of 400 mg do not reach an optimal response criteria according to the ELN (European Leukemia Net) recommendations. This has led to the exploration, as front-line therapy for CML, of second-generation tyrosine kinase inhibitors like nilotinib, dasatinib, and bosutinib, more powerful TKIs with respect to imatinib and initially registered as second-line therapy for the CML cases intolerant or resistant to imatinib. The clinical trials comparing imatinib versus the second generation TKIs have shown that the latter are able to induce faster and deeper molecular responses with respect to 400 mg imatinib, but these advantages are counterbalanced by a higher degree of immediate and long-term toxicities and by no improvement in the overall survival (OS) and progression-free survival (PFS) rates. In addition, more recently studies testing higher dosages of imatinib (800 mg per day) compared to standard dose imatinib or dose-adapted imatinib or imatinib plus interferon have been reported to be able to induce better cytogenetic and molecular responses, including the achievement of deep molecular responses like MR4 and MR4,5 which are needed to attempt treatment-free remission (TFR). Therefore, considering that imatinib has become a generic drug and that this has considerably lowered its cost allowing its use in patients all over the world, it is easy to understand why imatinib still represents the first-line therapy of choice for the majority of CML patients.