according to their response to prior interferon: failure to achieve (within 6 months), or loss of a complete hematologic response (29%), failure to achieve (within 1 year) or loss of a major cytogenetic response (35%), or intolerance to interferon (36%). Patients had received a median of 14 months of prior IFN therapy at doses ≥25 x 106 IU/week and were all in late chronic phase, with a median time from diagnosis of 32 months. Effectiveness was eva luated on the basis of the rate of hematologic response and by bone marrow exams to assess the rate of major cytogenetic response (up to 35% Ph+ metaphases) or complete cytogenetic response (0% Ph+ metaphases). Median duration of treatment was 29 months with 81% of patients treated for ≥24 months (maximum = 31.5 months). Efficacy results are reported in Table 15. Confirmed major cytogenetic response rates were higher in patients with IFN intolerance (66%) and cytogenetic failure (64%), than in patients with hematologic failure (47%). Hematologic response was achieved in 98% of patients with cytogenetic failure, 94% of patients with hematologic failure, and 92% of IFN-intolerant patients.
Accelerated Phase: 235 patients with accelerated phase disease were enrolled. These patients met one or more of the following criteria: ≥15%-<30% blasts in PB or BM; ≥30% blasts + promyelocytes in PB or BM; ≥20% basophils in PB; and <100 x 109/L platelets. The first 77 patients were started at 400 mg, with the remaining 158 patients starting at 600 mg.
Effectiveness was eva luated primarily on the basis of the rate of hematologic response, reported as either complete hematologic response, no evidence of leukemia (i.e., clearance of blasts from the marrow and the blood, but without a full peripheral blood recovery as for complete responses), or return to chronic phase CML. Cytogenetic responses were also eva luated. Median duration of treatment was 18 months with 45% of patients treated for ≥24 months (maximum=35 months). Efficacy results are reported in Table 15. Response rates in accelerated phase CML were higher for the 600 mg dose group than for the 400 mg group: hematologic response (75% vs. 64%), confirmed and unconfirmed major cytogenetic response (31% vs. 19%).
Myeloid Blast Crisis: 260 patients with myeloid blast crisis were enrolled. These patients had ≥30% blasts in PB or BM and/or extramedullary involvement other than spleen or liver; 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 remaining 223 patients were started at 600 mg.
Effectiveness was eva luated primarily on the basis of rate of hematologic response, reported as either complete hematologic response, no evidence of leukemia, or return to chronic phase CML using the same criteria as for the study in accelerated phase. Cytogenetic responses were also assessed. Median duration of treatment was 4 months with 21% of patients treated for ≥12 months and 10% for ≥24 months (maximum=35 months). Efficacy results are reported in Table 15. The hematologic response rate was higher in untreated patients than in treated patients (36% vs. 22%, respectively) and in the group receiving an initial dose of 600 mg rather than 400 mg (33% vs. 16%). The confirmed and unconfirmed major cytogenetic response rate was also higher for the 600 mg dose group than for the 400 mg do
