Updated data on CP-CML patients (n=270) from the ongoing trial indicate that with a median follow-up of 42.3 months (data as of February 2, 2015), 114 patients (42%) continue to receive ponatinib. Additional data in CP-CML patients include:
- 59% of CP-CML patients achieved MCyR (primary endpoint) at any time.
- 83% of patients who achieved MCyR are estimated to remain in MCyR at 3 years.
- 39% of patients achieved a major molecular response (MMR) or better.
- By Kaplan-Meier analysis, progression-free survival at 3 years is estimated to be 60%.
- Overall survival at 3 years is estimated to be 81%.
- 23% of CP-CML patients experienced an AOE designated a serious adverse event (SAE), and 28 percent of CP-CML patients experienced any AOE. The median time to onset for AOEs in CP-CML patients was 14.1 (0.3-44.0) months.
- 4% and 5% of CP-CML patients, respectively experienced a venous thromboembolic SAE or AE.
- The most common all-grade treatment-emergent adverse events occurring in = 40% of CP-CML patients were abdominal pain (46%), rash (46%), thrombocytopenia (45%), headache (43%), constipation (41%), and dry skin (41%); the discontinuation rate due to adverse events was 18% in CP-CML.
- CP-CML patients who already achieved a MCyR should have their ponatinib dose reduced to 15 mg/day,
- CP-CML patients who had not already achieved MCyR should have their dose reduced to 30 mg/day, and
- Advanced-phase patients should have their dose reduced to 30 mg/day.
- Of the 64 patients who were in MCyR as of October 10, 2013 and had a prospective dose reduction, 61 patients (95%) maintained their response at 1.3 years following prospective dose reduction.
- Of the 47 patients who were in MMR as of October 10, 2013 and had a prospective dose reduction, 44 patients (94%) maintained their response at 1.3 years following prospective dose reduction.
- 42 patients in MCyR did not undergo any dose reductions (the majority of which were already at a reduced dose of 30 mg or 15 mg as of October 10, 2013); of these, 39 patients (93%) maintained MCyR after 1.3 more years of ponatinib treatment.
- Of the patients who underwent prospective dose reduction, 5 of 71 patients (7%) without prior AOEs had a new AOE during the 1.3 year interval following prospective dose reduction.
- Of the patients who did not undergo prospective dose reduction, 9 of 67 patients (13%) without prior AOE had a new AOE in the same time interval.
In the U.S., Iclusig is a kinase inhibitor indicated for the:
- Treatment of adult patients with T315I-positive chronic myeloid leukemia (chronic phase, accelerated phase, or blast phase) or T315I-positive Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL).
- Treatment of adult patients with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia or Ph+ ALL for whom no other tyrosine kinase inhibitor (TKI) therapy is indicated.
- Vascular Occlusion: Arterial and venous thrombosis and occlusions have occurred in at least 27% of Iclusig treated patients, including fatal myocardial infarction, stroke, stenosis of large arterial vessels of the brain, severe peripheral vascular disease, and the need for urgent revascularization procedures. Patients with and without cardiovascular risk factors, including patients less than 50 years old, experienced these events. Monitor for evidence of thromboembolism and vascular occlusion. Interrupt or stop Iclusig immediately for vascular occlusion. A benefit risk consideration should guide a decision to restart Iclusig therapy.
- Heart Failure, including fatalities, occurred in 8% of Iclusig-treated patients. Monitor cardiac function. Interrupt or stop Iclusig for new or worsening heart failure.
- Hepatotoxicity, liver failure and death have occurred in Iclusig-treated patients. Monitor hepatic function. Interrupt Iclusig if hepatotoxicity is suspected.
Iclusig ® is a registered trademark of ARIAD Pharmaceuticals, Inc.