nib and inability to receive a higher dose due to toxicity. The definitions of resistance and intolerance to both dasatinib and nilotinib were similar to those for imatinib. The protocol was amended to exclude patients with a known history of the T315I mutation after 396 patients were enrolled in the trial.
The efficacy endpoints for patients with CP CML previously treated with one prior TKI (imatinib) were the rate of attaining MCyR at week 24 and the duration of MCyR. The efficacy endpoints for patients with CP CML previously treated with both imatinib and at least 1 additional TKI were the cumulative rate of attaining MCyR by week 24 and the duration of MCyR. The efficacy endpoints for patients with previously treated AP and BP CML were confirmed complete hematologic response (CHR) and overall hematologic response (OHR).
The trial enrolled 546 patients with CP, AP or BP CML. Of the total patient population 73% were imatinib resistant and 27% were imatinib intolerant. In this trial, 53% of patients were males, 65% were Caucasian, and 20% were 65 years old or older. Of the 546 treated patients, 503 were considered eva luable for efficacy. Patients were eva luable for efficacy if they had received at least one dose of BOSULIF and had a valid baseline efficacy assessment. Among eva luable patients, there were 266 patients with CP CML previously treated with one prior TKI (imatinib), 108 patients with CP CML previously treated with both imatinib and at least 1 additional TKI, and 129 patients with advanced phase CML previously treated with at least one TKI.
Median duration of BOSULIF treatment was 22 months in patients with CP CML previously treated with one TKI (imatinib), 8 months in patients with CP CML previously treated with imatinib and at least 1 additional TKI, 10 months in patients with AP CML previously treated with at least imatinib, and 3 months in patients with BP CML previously treated with at least imatinib.
The 24 week efficacy results are present in Table 6.
Table 6: Efficacy Results in Patients with Ph+ CP CML with Resistance to or Intolerance to Imatinib
Prior Treatment
with Imatinib Only
(N=266 eva luable)
n (%)
at 24 Weeks Prior Treatment with Imatinib and Dasatinib or Nilotinib
(N=108 eva luable)
n (%)
by 24 Weeks
Abbreviations: CI = confidence interval, MCyR = major cytogenetic response
Week 24
MCyR
(95% CI)
90 (33.8)
(28.2, 39.9)
29 (26.9)
(18.8, 36.2)
The minimum follow-up was 23 months for patients with CP CML treated with one prior TKI (imatinib) and 13 months for patients with CP CML treated with imatinib and at least one additional TKI. For the 53.4% of patients with CP CML treated with one prior TKI (imatinib) who achieved a MCyR at any time, the median duration of MCyR was not reached. Among these patients, 52.8 % had a MCyR lasting at least 18 months. For the 32.4% of patients with CP CML treated with imatinib and at least one additional TKI who achieved a MCyR at any time, the median duration of MCyR was not reached. Among these patients, 51.4% had a MCyR lasting at least 9 months. Of the 374 eva luable patients with CP CML, 16 patients had confirmed disease transformation to AP or BP while on treatment with BOSULIF.
The 48 week efficacy results in patients with accelerated and blast phases CML previously treated with at least imatinib are summarized in Table 7.
Table 7: Efficacy Results in Patients with Accelerated Phase and Blast Phase CML Previously Treated with at Least Imatinib
AP CML
(N=69 ev |
