Chronic phase chronic myeloid leukemia patients with low OCT-1 activityrandomised to high-dose imatinib achieve better responses, and lower failure rates, than those randomized to standard-dose.

Publication Type:

Journal Article

Source:

Haematologica, Volume 97, Issue 6, p.907-914 (2012)

Keywords:

2012, Center-Authored Paper, Clinical Research Division, January 2012, Public Health Sciences Division

Abstract:

Background. The functional activity of the OCT-1 protein (OCT-1 activity) is an excellent predictor of molecular response and progression free survival in newly diagnosed chronic phase chronic myeloid leukaemia patients treated with imatinib as front-line therapy. Design and Methods. In this study the predictive value of OCT-1 activity in the setting of 400 and 800mg/day imatinib dosing, and trough imatinib plasma levels are assessed in 100 patients enrolled to the TOPS study. Results. Patients on 400mg/day imatinib with high OCT-1 activity achieve significantly higher rates of major molecular response by 24 months than those patients with low OCT-1 activity (low OCT-1 activity -57% of patients;high OCT-1 activity 100%;p<0.001), but this difference does not reach significance in patients receiving 800mg/day (low OCT-1 activity -68%;high OCT-1 activity -95%;p=0.073). In addition, the combination of low trough imatinib levels (<1200ng/ml) and low OCT-1 activity defines a group of patients who achieve the lowest rates of major molecular response (47%) by 24 months when compared to all other patients (81% p=0.009). These patients are also at the highest risk for imatinib failure when compared to all other patients (p<0.001).Conclusions. High dose imatinib leads to superior molecular responses in patients with low OCT-1 activity. In this group trough imatinib levels may define a group with inferior outcomes. For high OCT-1 activity patients higher imatinib dosing or monitoring of imatinib trough levels were not found to be of significant clinical value. Hence OCT-1 activity determined prior to the start of therapy in newly diagnosed CML patients provides a valuable prognostic tool to determine the optimal up-front dose of imatinib in newly diagnosed chronic phase chronic myeloid leukaemia patients.