ematologic response, major cytogenetic response and complete cytogenetic response were also statistically significantly higher in the Gleevec arm compared to the IFN + Ara-C arm (no cross-over data considered for eva luation of responses). Median time to CCyR in the 454 responders was 6 months (range 2-64 months, 25th to 75th percentiles = 3 to 11 months) with 10% of responses seen only after 22 months of therapy).
Table 14 Response in Newly Diagnosed CML Study (84-Month Data) (Best Response Rate) Gleevec
n=553 IFN+Ara−C
n=553
Hematologic Response1
CHR Rate n (%) 534 (96.6%)* 313 (56.6%)*
[95% CI] [94.7%, 97.9%] [52.4%, 60.8%]
Cytogenetic Response2
Major Cytogenetic Response n (%) 472 (85.4 %)* 93 (16.8%)*
[95% CI] [82.1%, 88.2%] [13.8%, 20.2%]
Unconfirmed3 88.6%* 23.3%*
Complete Cytogenetic Response n (%) 413 (74.7%)* 36 (6.5%)*
[95% CI] [70.8, 78.3] [4.6, 8.9]
Unconfirmed3 82.5%* 11.6%*
*p<0.001, Fischer’s exact test
1Hematologic 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, no extramedullary involvement.
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.
Molecular response was defined as follows: in the peripheral blood, after 12 months of therapy, reduction of ≥3 logarithms in the amount of bcr-abl transcripts (measured by real-time quantitative reverse transcriptase PCR assay) over a standardized baseline. Molecular response was only eva luated in a subset of patients who had a complete cytogenetic response by 12 months or later (N = 333). The molecular response rate in patients who had a complete cytogenetic response in the Gleevec arm was 59% at 12 months and 72% at 24 months.
Physical, functional, and treatment-specific biologic response modifier scales from the FACT-BRM (Functional Assessment of Cancer Therapy - Biologic Response Modifier) instrument were used to assess patient-reported general effects of interferon toxicity in 1,067 patients with CML in chronic phase. After one month of therapy to six months of therapy, there was a 13%-21% decrease in median index from baseline in patients treated with IFN, consistent with increased symptoms of IFN toxicity. There was no apparent change from baseline in median index for patients treated with Gleevec.
Late Chronic Phase CML and Advanced Stage CML: Three international, open-label, single-arm phase 2 studies were conducted to determine the safety and efficacy of Gleevec in patients with Ph+ CML: 1) in the chronic phase after failure of IFN therapy, 2) in accelerated phase disease, or 3) in myeloid blast crisis. About 45% of patients were women and 6% were Black. In clinical studies 38%-40% of patients were ≥60 years of age and 10%-12% of patients were ≥70 years of age.
Chronic Phase, Prior Interferon-Alpha Treatment: 532 patients were treated at a starting dose of 400 mg; dose escalation to 600 mg was allowed. The patients were distributed in three main categories
