6.9 Hypereosinophilic Syndrome and Chronic Eosinophilic Leukemia
The safety profile in the HES/CEL patient population does not appear to be different from the safety profile of Gleevec observed in other hematologic malignancy populations, such as Ph+ CML. All patients experienced at least one adverse reaction, the most common being gastrointestinal, cutaneous and musculoskeletal disorders. Hematological abnormalities were also frequent, with instances of CTC Grade 3 leukopenia, neutropenia, lymphopenia and anemia.

6.10 Dermatofibrosarcoma Protuberans
Adverse reactions, regardless of relationship to study drug, that were reported in at least 10% of the 12 patients treated with Gleevec for DFSP in the phase 2 study are shown in Table 7.

Table 7 Adverse Reactions Reported in DFSP Patients in the Phase 2 Study (≥10% All Patients) All Grades Preferred term N=12
n (%)
Nausea 5 (41.7)
Diarrhea 3 (25.0)
Vomiting 3 (25.0)
Periorbital Edema 4 (33.3)
Face Edema 2 (16.7)
Rash 3 (25.0)
Fatigue 5 (41.7)
Edema Peripheral 4 (33.3)
Pyrexia 2 (16.7)
Eye Edema 4 (33.3)
Lacrimation Increased 3 (25.0)
Dyspnea Exertional 2 (16.7)
Anemia 3 (25.0)
Rhinitis 2 (16.7)
Anorexia 2 (16.7)

Clinically relevant or severe laboratory abnormalities in the 12 patients treated with Gleevec for DFSP in the phase 2 study are presented in Table 8.

Table 8 Laboratory Abnormalities Reported in DFSP Patients in the Phase 2 Study  N=12
CTC Grades1 Grade 3 Grade 4
Hematology Parameters  
- Anemia 17 % 0 %
- Thrombocytopenia 17 % 0 %
- Neutropenia 0 % 8 %
Biochemistry Parameters  
- Elevated Creatinine 0 % 8 %
1CTC Grades: neutropenia (Grade 3 ≥0.5-1.0 x 109/L, Grade 4 <0.5 x 109/L), thrombocytopenia (Grade 3 ≥10 - 50 x 109/L, Grade 4 <10 x 109/L), anemia (Grade 3 ≥65-80 g/L, Grade 4 <65 g/L), elevated creatinine (Grade 3 >3-6 x upper limit normal range [ULN], Grade 4 >6 x ULN), 

6.11 Gastrointestinal Stromal Tumors
Unresectable and/or Malignant Metastatic GIST

In the Phase 3 trials the majority of Gleevec-treated patients experienced adverse reactions at some time. The most frequently reported adverse reactions were edema, fatigue, nausea, abdominal pain, diarrhea, rash, vomiting, myalgia, anemia and anorexia. Drug was discontinued for adverse reactions in a total of 89 patients (5.4%). Superficial edema, most frequently periorbital or lower extremity edema was managed with diuretics, other supportive measures, or by reducing the dose of Gleevec [see Dosage and Administration (2.10)].Severe (CTC Grade 3/4)edema was observed in 182 patients (11.1%).

Adverse reactions, regardless of relationship to study drug, that were reported in at least 10% of the patients treated with Gleevec are shown in Table 9.

Overall the incidence of all grades of adverse reactions and the incidence of severe adverse reactions (CTC Grade 3 and above) were similar between the two treatment arms except for edema, which was reportedmore frequently in the 800 mg group.

Table 9 Number (%) of Patients with Adverse Reactions where Frequency is ≥10% in any One Group (Full Analysis Set) in the Phase 3Unresectable and/or Malignant Metastatic GIST Clinical Trials Reported or Specified Term Imatinib 400 mg
N=818 Imatinib 800 mg
N=822
 All Grades % Grades 3/4/5
% All Grades % Grades 3/4/5