Many of the medical and scientific terms used in this summary are found in the NCI Dictionary of Genetics Terms. When a linked term is clicked, the definition will appear in a separate window.
Creating evidence-based summaries on cancer genetics is challenging because the rapid evolution of new information often results in evidence that is incomplete or of limited quality. In addition, established methods for evaluating the quality of the evidence are available for some, but not all, aspects of...
A trial randomly assigning 1,106 previously untreated patients to imatinib mesylate or to interferon plus cytarabine documented a 76% complete cytogenetic response rate with imatinib mesylate versus 14% for interferon plus cytarabine at a median follow-up of 19 months.[1,2][Level of evidence: 1iiDiii] At 18 months, 96.7% of the imatinib group had avoided progression to accelerated-phase CML or blast crisis compared with 91.5% of the interferon plus cytarabine group (P < .001). Because 90% of the combination group had switched to imatinib by 18 months (mostly because of intolerance of side effects), a survival difference may never be observed. By the 5-year median follow-up of this trial, imatinib mesylate induced complete cytogenetic response in more than 80% of the participants, with the annual rate of progression to accelerated-phase CML or blast crisis dropping from 2% in the first year to less than 1% in the fourth year. In addition, the overall survival (OS) rate for all patients at 5 years is 89%, with fewer than 50% of all deaths (4.5%) caused by CML. More than 90% of completely responding patients still show detectable evidence of the BCR/ABL translocation, usually by reverse transcription-polymerase chain reaction (RT–PCR) or by fluorescence in situ hybridization of progenitor cell cultures.[3,4,5] The clinical implication of this finding after 10 years or more is unknown, but these results have changed clinical practice. Poor compliance is the predominant reason for inadequate molecular response to imatinib.
Tyrosine kinase inhibitors with greater potency and selectivity for BCR/ABL than imatinib have been evaluated in newly diagnosed patients with CML. In a randomized, prospective study of 846 patients comparing nilotinib with imatinib, the rate of major molecular response at 12 months was 43% and 44% for 2-dose schedules of nilotinib and 22% for imatinib (P < .001 for both comparisons). The rate of complete cytogenetic response at 12 months was 80% and 78% for 2-dose schedules of nilotinib and 65% for imatinib (P < .001 for both comparisons).[Level of evidence: 1iiDiv] Progression to accelerated-phase CML or blast crisis occurred in 11 patients on imatinib (4%) but only occurred in 2 patients (<1%, P = .01) and 1 patient (<1%, P = .004) for the patients on two-dose schedules of nilotinib.
Similarly, in a randomized, prospective study of 519 patients comparing dasatinib with imatinib, the rate of major molecular response at 12 months was 46% for dasatinib and 28% for imatinib (P < .0001). The rate of complete cytogenetic response at 12 months was 77% for dasatinib and 66% for imatinib (P = .007).[Level of evidence: 1iiDiv] Progression to accelerated-phase CML or blast crisis occurred in nine patients (3.5%) on imatinib and in five patients (1.9%) on dasatinib (not statistically different).