Nilotinib and Imatinib Mesylate in Patients with Ph+ CML

Orlando—According to 24-month follow-up data from a phase 3, randomized, open-label, multicenter trial, 150-mg capsules of nilotinib had better results than imatinib mesylate tablets when treating adult patients with chronic phase, newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). During an oral abstract session at the ASH meeting, Timothy Hughes, MD, MBBA, the study’s lead author, said nilotinib demonstrated superior complete cytogenetic response (CCyR), major molecular response (MMR), and complete molecular response, significantly fewer progressions to accelerated phase or blast crisis, and lower rates of suboptimal response and treatment failure. Dr. Hughes also said that both doses of nilotinib and imatinib were well tolerated. Nilotinib, a highly potent and selective inhibitor of BCR-ABL in vitro, is approved by the US Food and Drug Administration (FDA) to treat adult patients with newly diagnosed Ph+ CML in chronic phase. The ongoing ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials of Newly Diagnosed Ph+ CML Patients) trial is evaluating the safety and efficacy of nilotinib for first-line treatment of Ph+ CML in chronic phase. The ENESTnd study enrolled 846 patients at 217 sites in 35 countries who were randomized to receive 300 mg of nilotinib twice a day (n=282), 400 mg of nilotinib twice a day (n=281), or 400 mg of imatinib once a day (n=283). Nilotinib and imatinib are both oral therapies. At the 24-month follow-up, 74% of the first group was still receiving treatment compared with 78% in the second group and 67% in the third. The median time on treatment was 25.0 months, 25.7 months, and 24.7 months, respectively. The median dose intensity per day was 594 mg, 776 mg, and 400 mg, respectively. Both arms permitted nilotinib dose escalation, but imatinib dose escalation to 800 mg/day was only permitted for suboptimal response or treatment failure. Data presented at the ASH meeting showed nilotinib was more effective in the primary (rates of MMR) and secondary end points of CCyR and durable MMR rates. The researchers evaluated MMR by using a polymerase chain reaction blood test that detects BCR-ABL, a gene that causes Ph+ CML. They also utilized CCyR tests that require a bone marrow sample to detect cells containing the Philadelphia chromosome. Of the patients taking 300 mg of nilotinib twice daily, 71% achieved MMR compared with 67% of the nilotinib 400-mg twice-daily group and 44% of the imatinib group. The durable MMR rates were 42%, 39%, and 21%, respectively, while the rates of CCyR were 87%, 85%, and 77%, respectively. In addition, an estimated 98.0% of the 300-mg nilotinib group had progression-free survival compared with 97.7% for the 400-mg nilotinib group and 95.2% for the imatinib group. Nine patients in the 300-mg nilotinib arm died, including 5 related to CML, while 6 in the 400-mg nilotinib arm (3 CMLrelated) and 11 in the imatinib arm (10 CML-related) died. Nilotinib’s FDA labeling warns that the drug can cause QT prolongation that causes an irregular heartbeat and may lead to sudden death. Patients with hypokalemia, hypomagnesemia, and/or long QT syndrome should not take nilotinib. Serious side effects of the medication include low blood count, liver damage, pancreas inflammation, and bleeding in the brain.