New data from a large, international clinical trial find that patients with newly diagnosed chronic myeloid leukaemia who received Glivec (imatinib) at 800 mg/day as their initial treatment achieved clinical milestones significantly faster than those receiving the standard 400 mg/day dose.
The Tyrosine Kinase Inhibitor Optimization and Selectivity Study (TOPS) is the first phase III, randomized, controlled clinical trial designed to evaluate the potential benefits of an 800 mg starting dose across all risk categories of newly diagnosed, previously untreated patients with Philadelphia chromosome-positive chronic myeloid leukaemia (Ph+ CML).
Numerically, more patients achieved a major molecular response (MMR) with the 800 mg dose than the 400 mg dose (46.4% vs. 40.1%); however, the difference between the two arms — the primary endpoint of the study — was not statistically significant. This trend of improved MMR rate at 12 months in the 800 mg vs. 400 mg arms was most pronounced in the subset of patients with the highest risk for disease progression (41.1% vs. 26.2%). Further, patients in the 800 mg arm achieved MMR significantly faster than those who started treatment with Glivec at 400 mg. Achievement of a MMR is an important goal of therapy for CML.
TOPS also showed that patients with lower blood levels of Glivec at one month had a lower molecular response at a year, an observation made in previous studies. Cumulatively, these data suggest that maintaining adequate blood levels may help attain better clinical responses.