Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia: an analysis from the International Randomized Study of Interferon and STI571 (IRIS)

Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML)

“…Validation of the prognostic significance of 3-month molecular response An independent sample of 174 patients treated with imatinib within the International Randomized Study of Interferon and STI571 22 was used to validate the prognostic significance of 3-month molecular response. BCR-ABL IS p1% was observed in 64 patients (37%), 41-10% BCR-ABL IS in 67 patients (38%) and 410% BCR-ABL IS in 43 patients (25%).…”

“…4 Our CML Study IV data revealed the 1% BCR-ABL IS cutoff at 12 months to predict PFS and OS so far. 17 An evaluation of International Randomized Study of Interferon and STI571 data by Hughes et al 22 associated 10% BCR-ABL IS at 6 months and 1% BCR-ABL IS at 12 months with better event-free survival and PFS. According to our data, 1% and 10% BCR-ABL IS are predictive at 6 months with the 1% cutoff including more high-risk patients (Table 1).…”

HPLC–MS method for the simultaneous quantification of the antileukemia drugs imatinib, dasatinib and nilotinib in human peripheral blood mononuclear cell (PBMC)

“…In the International Randomized Study of Interferon and STI571 (IRIS; ClinicalTrials.gov number, NCT00006343), imatinib has been associated with a superior response rate and improved progression-free survival, as compared with the previous standard therapy, interferon alfa plus lowdose cytarabine [5][6][7]. Eight-year follow-up of IRIS revealed that responses to imatinib were durable and had an acceptable adverse-event profile, with an estimated rate of overall survival of 85% [8]. Although most patients show excellent responses to imatinib treatment, nearly 20% of patients who take the drug do not have a complete cytogenetic response, and others may have intolerable side effects or drug resistance over time [8].…”

“…Eight-year follow-up of IRIS revealed that responses to imatinib were durable and had an acceptable adverse-event profile, with an estimated rate of overall survival of 85% [8]. Although most patients show excellent responses to imatinib treatment, nearly 20% of patients who take the drug do not have a complete cytogenetic response, and others may have intolerable side effects or drug resistance over time [8]. Resistance, mainly caused by point mutations, leads to a reduced affinity of imatinib for the ATP binding domain of the BCR-ABL protein and to a reactivation of the BCR-ABL kinase activity [9][10].…”

“…Resistance, mainly caused by point mutations, leads to a reduced affinity of imatinib for the ATP binding domain of the BCR-ABL protein and to a reactivation of the BCR-ABL kinase activity [9][10]. Loss of response and transformation to advanced disease occur mainly in the first 3 years of imatinib therapy, inducing a rate of overall survival often poor in these patients [8]. To overcome imatinib resistance and intolerance, more potent tyrosine kinase inhibitors (TKIs), such as dasatinib and nilotinib, have been developed for the treatment of CML.…”