ation of treatment with Iclusig was 337 days in patients with chronic phase CP-CML, 362 days in patients with accelerated phase AP-CML, 89 days in patients with BP-CML, and 81 days in patients with Ph+ALL. The median dose intensity was 37 mg or, 83% of the expected 45 mg dose.
Adverse reactions reported in more than 10% of all patients treated with Iclusig in this trial are presented in Table 4. Overall, the most common non-hematologic adverse reactions (≥ 20%) were hypertension, rash, abdominal pain, fatigue, headache, dry skin, constipation, arthralgia, and nausea, and pyrexia.
The rates of treatment-emergent adverse events resulting in discontinuation were 13% in CP-CML, 11% in AP-CML, 15% in BP-CML, and 9% in Ph+ALL. The most common adverse events that led to treatment discontinuation were thrombocytopenia (4%) and infections (1%).
Dose modifications (dose delays or dose reduction) due to adverse reactions occurred in 74% of the patients. The most common adverse reactions (≥5%) that led to dose modifications include thrombocytopenia (30%), neutropenia (13%), lipase increased (12%), rash (11%), abdominal pain (11%), pancreatitis (6%), and ALT, AST, or GGT increased (6%).
Table 4: Adverse Reactions Occurring in >10% of Patients, Any Group CP-CML
(N=270) AP-CML
(N=85) BP-CML
(N=62) Ph+ ALL
(N=32)
System Organ Class Any Grade
(%) CTCAE Grade
3 / 4
(%) Any Grade
(%) CTCAE Grade
3 / 4
(%) Any Grade
(%) CTCAE Grade
3 / 4
(%) Any Grade
(%) CTCAE Grade
3 / 4
(%)
Cardiac or Vascular disorders
Hypertension * 68 39 71 36 65 26 53 31
Arterial ischemia † 13 7 12 6 8 5 3 0
Cardiac Failure ‡ 6 4 6 2 15 11 6 6
Gastrointestinal disorders
Abdominal pain § 49 10 40 8 34 6 44 6
Constipation 37 2 24 2 26 0 47 3
Nausea 23 1 27 0 32 2 22 0
Diarrhea 16 1 26 0 18 3 13 3
Vomiting 13 2 24 0 23 2 22 0
Oral mucositis ¶ 10 1 15 1 23 0 9 3
GI hemorrhage # 2 <1 8 1 11 5 9 6
Blood and lymphatic system disorders
Febrile neutropenia 1 <1 4 4 11 11 25 25
Infections and infestations
Sepsis 1 1 5 5 8 8 22 22
Pneumonia 3 2 11 9 13 11 9 3
Urinary tract infection 7 1 12 1 0 0 9 0
Upper respiratory tract infection 11 1 8 0 11 2 0 0
Nasopharyngitis 9 0 12 0 3 0 3 0
Cellulitis 2 1 4 2 11 3 0 0
Nervous system disorders
Headache 39 3 28 0 31 3 25 0
Peripheral neuropathy Þ 13 2 8 0 8 0 6 0
Dizziness 11 0 5 0 5 0 3 0
Respiratory, thoracic, and mediastinal disorders
Pleural effusion 3 1 11 2 13 0 19 3
Cough 12 0 17 0 18 0 6 0
Dyspnea 11 2 15 2 21 7 6 0
Skin and subcutaneous tissue disorders
Rash and related conditions 54 5 48 8 39 5 34 6
Dry skin 39 2 27 1 24 2 25 0
Musculoskeletal and connective tissue disorders
Arthralgia 26 2 31 1 19 0 13 0
Myalgia 22 1 20 0 16 0 6 0
Pain in extremity 17 2 17 0 13 0 9 0
Back pain 15 1 11 2 16 2 13 0
Muscle spasms 12 0 5 0 5 0 13 0
