Major response n (%)
 490 (88.6%)*
 129 (23.3%)*
 
[95% CI]
 [85.7%, 91.1%]
 [19.9%, 27.1%]
 
Complete CyR n (%)
 456 (82.5%)*
 64 (11.6%)*
 
Partial CyR n (%)
 34 (6.1%)
 65 (11.8%)
 
Molecular response**
    
Major response at 12 months (%)
 153/305=50.2%
 8/83=9.6%
 
Major response at 24 months (%)
 73/104=70.2%
 3/12=25%
 
Major response at 84 months (%)
 102/116=87.9%
 3/4=75%
 
* p<0.001, Fischer's exact test
** molecular response percentages are based on available samples
Haematological response criteria (all responses to be confirmed after ≥ 4 weeks):
WBC < 10 x 109/l, platelet < 450 x 109/l, myelocyte+metamyelocyte < 5% in blood, no blasts and promyelocytes in blood, basophils < 20%, no extramedullary involvement
Cytogenetic response criteria: complete (0% Ph+ metaphases), partial (1–35%), minor (36–65%) or minimal (66–95%). A major response (0–35%) combines both complete and partial responses.
Major molecular response criteria: in the peripheral blood reduction of ≥ 3 logarithms in the amount of Bcr-Abl transcripts (measured by real-time quantitative reverse transcriptase PCR assay) over a standardised baseline.
Rates of complete haematological response, major cytogenetic response and complete cytogenetic response on first-line treatment were estimated using the Kaplan-Meier approach, for which non-responses were censored at the date of last examination. Using this approach, the estimated cumulative response rates for first-line treatment with Glivec improved from 12 months of therapy to 84 months of therapy as follows: CHR from 96.4% to 98.4% and CCyR from 69.5% to 87.2%, respectively.
With 7 years follow-up, there were 93 (16.8%) progression events in the Glivec arm: 37 (6.7%) involving progression to accelerated phase/blast crisis, 31 (5.6%) loss of MCyR, 15 (2.7%) loss of CHR or increase in WBC, and 10 (1.8%) CML unrelated deaths. In contrast, there were 165 (29.8%) events in the IFN+Ara-C arm, of which 130 occurred during first-line treatment with IFN+Ara-C.
The estimated rate of patients free of progression to accelerated phase or blast crisis at 84 months was significantly higher in the Glivec arm compared to the IFN arm (92.5% versus 85.1%, p<0.001). The annual rate of progression to accelerated phase or blast crisis decreased with time on therapy and was less than 1% annually in the fourth and fifth years. The estimated rate of progression-free survival at 84 months was 81.2% in the Glivec arm and 60.6% in the control arm (p<0.001). The yearly rates of progression of any type for Glivec also decreased over time.
A total of 71 (12.8%) and 85 (15.4%) patients died in the Glivec and IFN+Ara-C groups, respectively. At 84 months the estimated overall survival is 86.4% (83, 90) vs. 83.3% (80, 87) in the randomised Glivec and the IFN+Ara-C groups, respectively (p=0.073, log-rank test). This time-to-event endpoint is strongly affected by the high crossover rate from IFN+Ara-C to Glivec. The effect of Glivec treatment on survival in chronic phase, newly diagnosed CML has been further examined in a retrospective analysis of the above reported Glivec data with the primary data from another Phase III study using IFN+Ara-C (n=325) i