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 Leukemia
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 14patients with Hypereosinophilic Syndrome/Chronic Eosinophilic Leukemia (HES/CEL). HES patients were treated with 100mg to 1000mg of Gleevec daily. The ages of these patients ranged from 16 to 64years. A further 162patients with HES/CEL aged 11 to 78years were reported in 35published case reports and case series. These patients received Gleevec at doses of 75mg to 800mg daily. Hematologic response rates are summarized in Table 19. Response durations for literature patients ranged from 6+ weeks to 44 months.

Table 19 Response in HES/CEL Cytogenetic Abnormality Number of Patients Complete Hematological Response
N (%) Partial Hematological Response
N (%)
Positive FIP1L1-PDGFRα Fusion Kinase  61 61 (100%) 0%
Negative FIP1L1-PDGFRα Fusion Kinase  56 12 (21%) 9 (16%)
Unknown Cytogenetic Abnormality  59 34 (58%) 7 (12%)
Total 176 107 (61%) 23 (13%)

14.7 Dermatofibrosarcoma ProtuberansDermatofibrosarcoma Protuberans (DFSP) is a cutaneous soft tissue sarcoma. It is characterized by a translocation of chromosomes 17 and 22 that results in the fusion of the collagen type 1 alpha 1 gene and the PDGF B gene.

An open-label, multicenter, phase 2 study was conducted testing Gleevec in a diverse population of patients with life-threatening diseases associated with Abl, Kit or PDGFR protein tyrosine kinases. This study included 12 patients with DFSP who were treated with Gleevec 800 mg daily (age range 23 to 75 years). DFSP was metastatic, locally recurrent following initial surgical resection and not considered amenable to further surgery at the time of study entry. A further 6 DFSP patients treated with Gleevec are reported in 5 published case reports, their ages ranging from 18 months to 49 years. The total population treated for DFSP therefore comprises 18 patients, 8 of them with metastatic disease. The adult patients reported in the published literature were treated with either 400 mg (4 cases) or 800 mg (1 case) Gleevec daily. A single pediatric patient received 400 mg/m2/daily, subsequently increased to 520 mg/m2/daily. Ten patients had the PDGF B gene rearrangement, 5 had no available cytogenetics and 3 had compl