ORLANDO, FLA—Treatment with nilotinib(Drug information on nilotinib) (Tasigna) turned in very low failure rates, stable responses, and very high rates of response achieved during the first 12 months of treatment in early chronic phase Philadelphia-positive chronic myeloid leukemia (Ph+ CML). The leader of the GIMEMA* CML Working Party called nilotinib "more potent and more selective" than imatinib(Drug information on imatinib) (Gleevec) in this patient population.

"CML was a deadly disease, there is no doubt about it, and in the last 10 years imatinib has dramatically improved survival. But some problems remain, particularly in the first three years after starting imatinib treatment," said Gianantonio Rosti, MD, scientific secretary of the GIMEMA CML Working Party and a professor of hematology and oncology at the University of Bologna in Italy.

"Nilotinib versus imatinib is simply more potent and more selective and is able to rescue 50% of patients who become resistant to imatinib. We wanted to evaluate its effectiveness as a first-line treatment in Ph+ CML patients," Dr. Rosti said.

Being able to confirm the durability of nilotinib responses also was extremely important. "The fear we had a couple years ago was that we would see very good responses in the early period of treatment with nilotinib, but there was a lot of uncertainty about the event-free and overall survival later on," Dr. Rosti said. "It is over that three-year time period that most of the failures to imatinib are described."

The multicenter phase II trial enrolled 73 patients (median age 51 years) newly diagnosed with Ph+ CML. Patients received nilotinib 400 mg twice a day. Forty-three percent were deemed low Sokal risk, 41% intermediate risk, and 14% high risk.

The primary endpoint of the study was the complete cytogenetic response (CCyR) rate at 12 months. The study also evaluated overall survival (OS), progression-free survival (PFS), treatment failure-free survival, and event-free survival (EFS).

The CCyR rate was high at each of the different time points throughout the study. At three months, it was 78% and by six months it was 96%. It remained at that level for 12 and 18 months, and then dropped slightly to 92% at 24 months, Dr. Rosti reported. The cumulative CCyR rate for patients in the trial was 100% by 12 months. "This means that all patients achieved a complete cytogenetic response at least once," he noted.

At a median follow-up of 36 months, the OS, PFS, and failure-free survival rates reached 99% in all three categories; EFS was 92%. The cumulative major molecular response (MMR) rate was 96% at 12 months, while the MMR rates at three, six, 12, 18, and 24 months were 52%, 66%, 85%, 81%, and 82%, respectively (ASH 2010 abstract 359).

The cumulative rate of complete molecular response (CMR) was 41%. Broken down, the CMR rate was 7% at 12 months and 12% at 24 months. None of the patients who achieved an MMR progressed to accelerated phase or blast crisis. Only one patient progressed to accelerated phase/blast crisis at six months, Dr. Rosti reported. This was a 63-year-old woman with high Sokal risk disease in complete cytogenetic response at three months who developed a T3151 mutation.

The adverse events reported in the study were mostly grade 1 or 2 and manageable with dose modification, Dr. Rosti said. Among these adverse events were two patients (3% of the study cohort) who showed prolonged QT interval. In addition, three patients discontinued treatment with nilotinib because of recurrent episodes of amylase or lipase increases. One patient discontinued after 25 months due to atrial fibrillation, which was unrelated to nilotinib.

"Even after three years of treatment, the number of failures, especially progression to blast crisis, is still one out of 73. This is reassuring news indeed," he said.


*GIMEMA = Gruppo Italiano Malattie Ematologiche dell'Adulto