Evidence of Leukemia (NEL) Not applicable 13% 5%
Return to Chronic Phase (RTC) Not applicable 20% 18%
Major Cytogenetic Response2 60% [55.3−63.8] 21% [16.2−27.1] 7% [4.5−11.2]
(Unconfirmed3) (65%) (27%) (15%)
Complete4 (Unconfirmed3) 39%(47%) 16%(20%) 2%(7%)
1Hematologic response criteria (all responses to be confirmed after ≥4 weeks):
CHR:Chronic phase study [WBC <10 x 109/L, platelet <450 x 109/L, myelocytes + metamyelocytes <5% in blood, no blasts and promyelocytes in blood, basophils <20%, no extramedullary involvement] and in the accelerated and blast crisis studies [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 (accelerated and blast crisis studies)
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 (accelerated and blast crisis studies).
BM=bone marrow, PB=peripheral blood
2Cytogenetic response criteria (confirmed after ≥4 weeks): complete (0% Ph+ metaphases) or partial (1%-35%). A major response (0%-35%) combines both complete and partial responses.
3Unconfirmed cytogenetic response is based on a single bone marrow cytogenetic eva luation, therefore unconfirmed complete or partial cytogenetic responses might have had a lesser cytogenetic response on a subsequent bone marrow eva luation.
4 Complete cytogenetic response confirmed by a second bone marrow cytogenetic eva luation performed at least 1 month after the initial bone marrow study.
The median time to hematologic response was 1 month. In late chronic phase CML, with a median time from diagnosis of 32 months, an estimated 87.8% of patients who achieved MCyR maintained their response 2 years after achieving their initial response.After 2 years of treatment, an estimated 85.4% of patients were free of progression to AP or BC, andestimated overall survival was 90.8% [88.3, 93.2].In accelerated phase, median duration of hematologic response was 28.8 months for patients with an initial dose of 600 mg (16.5 months for 400 mg). An estimated 63.8% of patients who achieved MCyR were still in response 2 years after achieving initial response. The median survival was 20.9 [13.1, 34.4] months for the 400mg group and was not yet reached for the 600mg group (p=0.0097). An estimated 46.2% [34.7, 57.7] vs. 65.8% [58.4, 73.3] of patients were still alive after 2 years of treatment in the 400mg vs. 600mg dose groups, respectively. In blast crisis, the estimated median duration of hematologic response is 10 months. An estimated 27.2% [16.8, 37.7] of hematologic responders maintained their response 2 years after achieving their initial response. Median survival was 6.9 [5.8, 8.6] months, and an estimated 18.3% [13.4, 23.3] of all patients with blast crisis were alive 2 years after start of study.
Efficacy results were similar in men and women and in patients younger and older than age 65. Responses were seen in Black patients, but there were too few Black patients to allow a quantitative comparison.
14.2 Pediatric CML
A total of 51 pediatric patients with newly diagnosed and untreated CML in chronic phase were enrolled in an open-label, multicenter, single arm phase 2 trial. Patients were treated with Gleevec 340 mg/m2/day, with no interruptions in the absence of dose limiting toxicit
