The Efficacy and Tolerability of Generic of Imatinib in a Very Specific Group of Chronic Myeloid Leukemia

S36 follow-up: 34.2 (0.1e48.6) months, overall; 38.4 (0.1e48.6) months, CP-CML. Setting: Multicenter study. Patients: CML/Ph+ ALL resistant/intolerant to dasatinib/nilotinib or with T315I (N1⁄4449). Intervention: Ponatinib (starting dose, 45 mg qd). Main Outcome Measures: Response, PFS, OS, AEs. Results: Patients were heavily pretreated, 58% with 3 TKIs. At analysis, 33% of all patients and 45% of CP-CML patients remained on study. Primary reasons for discontinuation: progression (21% overall, 9% CP-CML); AEs (15% overall, 17% CP-CML). Among CP-CML patients: 59% achievedMCyR; 39% achievedMMRor better; 22% achievedMR4.5. For CP-CML, estimated probability of maintaining MCyR at 3 years: 83%; estimated 3-year PFS: 61%. Estimated 3-year OS: 82% (CPCML); 59% (AP-CML); 9% (BP-CML); 16% (Ph+ ALL). Treatmentemergent AEs in 25% of patients: thrombocytopenia (43%), abdominal pain (42%), rash (41%), constipation (37%), headache (37%), dry skin (36%), fatigue (30%), pyrexia (29%), arthralgia (29%), hypertension (28%), nausea (28%), and neutropenia (25%). Arterial occlusive events (AOEs) led to recommendeddose reduction inOctober 2013. AOE (any/serious) rates: 22%/17%, including cardiovascular (12%/8%), cerebrovascular (8%/6%), and peripheral vascular (8%/ 6%); venous thromboembolic event (VTE; any/serious) rates: 5%/4%. Of patients with AOEs (n1⁄499), 42 remained on study; 33 maintained MCyR. Exposure-adjusted incidence rates of new AOEs/VTEs (events per 100 patient-years): 14.5/3.5 (Year 1); 14.1/1.8 (Year 2); 10.8/1.8 (Year 3). One year after recommended dose reduction: 61/64 (95%) CP-CML patients maintainedMCyR; 44/47 (94%) CP-CML patients maintained MMR; 5/70 (7%) of all ongoing patients without a prior AOE had an AOE. Conclusions: Ponatinib continues to provide benefit to heavily pretreated patients, particularly CP-CML patients. One year after recommended dose reduction, patients maintained responses, and incidence of new AOEs was lower than in previous years. A dose-ranging trial of ponatinib in refractory CML will open soon. This study was sponsored by ARIAD Pharmaceuticals, Inc.