y not reflect the rates observed in practice.
Serious adverse reactions reported include anaphylactic shock [see Contraindications (4)], myelosuppression, gastrointestinal toxicity (diarrhea), fluid retention, hepatoxicity and rash.
Adverse reactions of any toxicity grade reported for greater than 20% of patients in the Phase 1/2 safety population (n=546) were diarrhea (82%), nausea (46%), thrombocytopenia (41%), vomiting (39%), abdominal pain (37%), rash (35%), anemia (27%), pyrexia (26%), and fatigue (24%).
6.1 Imatinib-Resistant or -Intolerant Ph+ Chronic Phase (CP), Accelerated Phase (AP), and Blast Phase (BP) CML
The single-arm Phase 1/2 clinical trial enrolled patients with Ph+ chronic, accelerated, or blast phase chronic myelogenous leukemia (CML) and Ph+ acute lymphoblastic leukemia (ALL) with resistance or intolerance to prior therapy. The safety population (received at least 1 dose of BOSULIF) included 546 CML patients. Within the safety population there were 287 patients with CP CML previously treated with imatinib only who had a median duration of BOSULIF treatment of 24 months, and a median dose intensity of 484 mg/day. There were 119 patients with CP CML previously treated with both imatinib and at least 1 additional TKI who had a median duration of BOSULIF treatment of 9 months and a median dose intensity of 475 mg/day. There were 76 patients with AP CML, and 64 patients with BP CML. In the patients with AP CML and BP CML, the median duration of BOSULIF treatment was 10 months and 3 months, respectively. The median dose intensity was 483 mg/day, and 500 mg/day, in the AP CML and BP CML cohorts, respectively.
Table 2 identifies adverse reactions greater than or equal to 10% for all grades and grades 3 or 4 for the Phase 1/2 CML safety population.
Table 2: Adverse Reactions (10% or greater) in patients with CML
System Organ Class
Preferred Term CP CML
N=406
n (%) AdvP CML
N=140
n (%) All CP and AdvP CML
N=546
n (%)
All Grades Grade 3/4 All Grades Grade 3/4 All Grades Grade 3/4
CP CML = Chronic Phase CML; AdvP CML = Advanced Phase CML (includes patients with Accelerated Phase and Blast Phase CML)
*
Abdominal pain includes the following preferred terms: Abdominal pain, Abdominal pain upper, Abdominal pain lower, Abdominal tenderness, Gastrointestinal pain, Abdominal discomfort
†
Fatigue includes the following preferred terms: Fatigue, Malaise
‡
Edema includes the following preferred terms: Edema, Edema peripheral, Localized edema, Face edema
§
Respiratory tract infection includes the following preferred terms: Respiratory tract infection, Upper respiratory tract infection, Lower respiratory tract infection, Viral upper respiratory tract infection, Respiratory tract infection viral
¶
Rash includes the following preferred terms: Rash, Rash macular, Rash pruritic, Rash generalized, Rash papular, Rash maculo-papular
Gastrointestinal Disorders
Diarrhea 342 (84) 38 (9) 107 (76) 7 (5) 449 (82) 45 (8)
Nausea 186 (46) 5 (1) 66 (47) 3 (2) 252 (46) 8 (1)
Abdominal Pain* 162 (40) 6 (1) 41 (29) 7 (5) 203 (37) 13 (2)
Vomiting 152 (37) 12 (3) 59 (42) 5 (4) 211 (39) |
