n molecular relapse after bone marrow transplant responded molecularly. Median duration of therapy was 12.9 months (0.8-26.7) in the 7 patients treated within the phase 2 study and ranged between 1 week and more than 18 months in responding patients in the published literature. Results are provided in Table 17.Response durations of phase 2 study patients ranged from 141+ days to 457+ days.
Table 17 Response in MDS/MPD CompleteHematologic Response Major Cytogenetic Response
N N (%) N (%)
Overall Population 31 14 (45) 12 (39)
Chromosome 5 Translocation 14 11 (79) 11 (79)
Chromosome 4 Translocation 2 2 (100) 1 (50)
Others / no Translocation 14 1 (7) 0 (0)
Molecular Relapse 1 NE1 NE1
1NE: Not eva luable
14.5 Aggressive Systemic Mastocytosis
One open-label, multicenter, phase 2 study was conducted testing Gleevec in diverse populations of patients with life-threatening diseases associated with Abl, Kit or PDGFR protein tyrosine kinases.This study included 5patients with aggressive systemic mastocytosis (ASM)treated with 100 mg to 400 mg of Gleevec daily.These 5 patients ranged from 49 to 74years of age. In addition to these 5 patients, 10 published case reports and case series describe the use of Gleevec in 23additional patients with ASM aged 26 to 85years who also received 100 mg to 400 mg of Gleevec daily.
Cytogenetic abnormalities were eva luated in 20 of the 28ASM patients treated with Gleevec from the published reports and in the phase 2 study.Seven of these 20patients had the FIP1L1-PDGFRα fusion kinase (or CHIC2 deletion). Patients with this cytogenetic abnormality were predominantly males and had eosinophilia associated with their systemic mast cell disease.Two patients had a Kit mutation in the juxtamembrane region (one Phe522Cys and one K509I) and four patients had a D816V c-Kit mutation (not considered sensitive to Gleevec), one with concomitant CML.
Of the 28patients treated for ASM, 8 (29%) achieved a complete hematologic response and 9 (32%) a partial hematologic response (61% overall response rate).Median duration of Gleevec therapy for the 5 ASM patients in the phase 2 study was 13months (range 1.4-22.3months) and between 1month and more than 30months in the responding patients described in the published medical literature.A summary of the response rates to Gleevec in ASM is provided in Table18.Response durations of literature patients ranged from 1+ to 30+ months.
Table 18 Response in ASM Cytogenetic Abnormality Number of Patients Complete Hematologic Response
N (%) Partial Hematologic Response
N (%)
FIP1L1-PDGFRα Fusion Kinase (or CHIC2 Deletion) 7 7(100%) 0%
Juxtamembrane Mutation 2 0 (0%) 2 (100%)
Unknown or No Cytogenetic Abnormality Detected 15 0(0%) 7 (44%)
D816V Mutation 4 1* (25%) 0%
Total 28 8 (29%) 9 (32%)
*Patient had concomitant CML and ASM
Gleevec has not been shown to be effective in patients with less aggressive forms of systemic mastocytosis (SM). Gleevec is therefore not recommended for use in patients with cutaneous mastocytosis, indolent systemic mastocytosis (smoldering SM or isolated bone marrow mastocytosis),SM with an associated clonal hematological non-mast cell lineage disease, mast cell leukemia, mast cell sarcoma or extracutaneous mastocytoma. Patients that harbor the D816V mutation of c-Kit are not sensitive to Gleevec and should not receive Gleevec.
14.6 Hypereosinophilic Syndrome/Chronic Eosinophilic Leukemi
