nths, respectively.
Myeloid blast crisis: 260 patients with myeloid blast crisis were enrolled. 95 (37%) had received prior chemotherapy for treatment of either accelerated phase or blast crisis (“pretreated patients”) whereas 165 (63%) had not (“untreated patients”). The first 37 patients were started at 400 mg, the protocol was subsequently amended to allow higher dosing and the remaining 223 patients were started at 600 mg.
The primary efficacy variable was the rate of haematological response, reported as either complete haematological response, no evidence of leukaemia, or return to chronic phase CML using the same criteria as for the study in accelerated phase. In this study, 31% of patients achieved a haematological response (36% in previously untreated patients and 22% in previously treated patients). The rate of response was also higher in the patients treated at 600 mg (33%) as compared to the patients treated at 400 mg (16%, p=0.0220). The current estimate of the median survival of the previously untreated and treated patients was 7.7 and 4.7 months, respectively.
Lymphoid blast crisis: a limited number of patients were enrolled in phase I studies (n=10). The rate of haematological response was 70% with a duration of 2-3 months.
Table 4 Response in adult CML studies
Study 0110
37-month data
Chronic phase, IFN failure
(n=532)
Study 0109
40.5-month data
Accelerated phase
(n=235)
Study 0102
38-month data
Myeloid blast crisis
(n=260)
% of patients (CI95%)
Haematological response1
95% (92.3-96.3)
71% (65.3-77.2)
31% (25.2-36.8)
Complete haematological response (CHR)
95%
42%
8%
No evidence of leukaemia (NEL)
Not applicable
12%
5%
Return to chronic phase (RTC)
Not applicable
17%
18%
Major cytogenetic response2
65% (61.2-69.5)
28% (22.0-33.9)
15% (11.2–20.4)
Complete
53%
20%
7%
(Confirmed3) [95% CI]
(43%) [38.6-47.2]
(16%) [11.3-21.0]
(2%) [0.6-4.4]
Partial
12%
7%
8%
1 Haematological response criteria (all responses to be confirmed after ≥ 4 weeks):
CHR: Study 0110 [WBC < 10 x 109/l, platelets < 450 x 109/l, myelocyte+metamyelocyte < 5% in blood, no blasts and promyelocytes in blood, basophils < 20%, no extramedullary involvement] and in studies 0102 and 0109 [ANC ≥ 1.5 x 109/l, platelets ≥ 100 x 109/l, no blood blasts, BM blasts < 5% and no extramedullary disease]
NEL Same criteria as for CHR but ANC ≥ 1 x 109/l and platelets ≥ 20 x 109/l (0102 and 0109 only)
RTC < 15% blasts BM and PB, < 30% blasts+promyelocytes in BM and PB, < 20% basophils in PB, no extramedullary disease other than spleen and liver (only for 0102 and 0109).
BM = bone marrow, PB = peripheral blood
2 Cytogenetic response criteria:
A major response combines both complete and partial responses: complete (0% Ph+ metaphases), partial (1–35%)
3 Complete cytogenetic response confirmed by a second bone marrow cytogenetic eva luation performed at least one month after the initial bone marrow study.
Paediatric patients: A total
