ribution were reported for 100% patients with accelerated phase CML. A total of 33% of patients had adverse reactions leading to withdrawal. The most frequently occurring adverse reactions leading to withdrawal were leukocytosis (6%), and thrombocytopenia (4%). A total of 84% of patients reported at least 1 Grade 3 or Grade 4 treatment emergent adverse reaction (Table 2).
Table 2: Adverse Reactions Occurringa in at Least 10% of Patients
(Chronic Myeloid Leukemia – Accelerated Phase)
Number (%) of Patients
(N=55)
Adverse reactions
All reactions
Grade 3 or 4 reactions
Patients with at least 1 commonly occurring adverse reaction
55 (100)
46 (84)
Blood and Lymphatic System Disorders
Anemia
28 (51)
20 (36)
Febrile Neutropenia
11 (20)
9 (16)
Neutropenia
11 (20)
10 (18)
Thrombocytopenia
31 (56)
27 (49)
Gastrointestinal Disorders
Diarrhea
19 (35)
4 (7)
Nausea
15 (27)
2 (4)
Vomiting
8 (15)
1 (2)
Abdominal Pain
7 (13)
0
General Disorders and Administration Site Conditions
Fatigue
17 (31)
5 (9)
Pyrexia
16 (29)
1 (2)
Asthenia
13 (24)
1 (2)
Chills
7 (13)
0
Infusion and injection site related reactions
12 (22)
0
Infections and Infestationsb
31 (56)
11 (20)
Metabolism and Nutrition Disorders
Anorexia
7 (13)
1 (2)
Musculoskeletal and Connective Tissue Disorders
Pain in Extremity
6 (11)
1 (2)
Nervous System Disorders
Headache
7 (13)
0
Respiratory, Thoracic and Mediastinal Disorders
Cough
8 (15)
0
Dyspnea
6 (11)
1 (2)
Epistaxis
6 (11)
1 (2)
a Occurred in the period between the first dose and 30 days after the last dose.
b Infection includes bacterial, viral, fungal, and non-specified.
Serious adverse reactions were reported for 60% of patients. Serious adverse reactions reported for at least 5% of patients were febrile neutropenia (18%), thrombocytopenia (9%), anemia (7%), diarrhea and convulsions (6% each). Serious adverse reactions of infections were reported for 11% of patients. Death occurred while on study in 5 (9%) patients with AP CML. Two patients died due to cerebral hemorrhage and three due to progression of disease.
Laboratory Abnormalities in Chronic and Accelerated Phase CML
Grade 3/4 laboratory abnormalities reported in patients with chronic and accelerated phase CML are described in Table 3. Myelosuppression occurred in all patients treated with SYNRIBO. [see Warnings and Precautions (5.1)] Five patients with chronic phase CML and 4 patients with accelerated phase CML permanently discontinued SYNRIBO due to pancytopenia, thrombocytopenia, febrile neutropenia, or bone marrow necrosis. An event of hyperosmolar non-ketotic hyperglycemia was reported in one patient in the safety population and a similar case has been reported in the literature. Two patients with chronic phase CML permanently discontinued SYNRIBO due to elevated transaminases.
Table 3: Grade 3/4 Laboratory Abnormalities in Clinical Studies in Patients
with Chronic Phase and Ac
