Effectiveness and safety of nilotinib in chronic phase chronic myeloid leukemia

This study examined the effectiveness of different doses of nilotinib (Tasigna) in patients with newly diagnosed chronic myeloid leukemia in chronic phase. This study concluded that nilotinib was safe and effective in treating chronic myeloid leukemia. 

Chronic myeloid leukemia is a cancer where the bone marrow makes too many white blood cells. In chronic phase, the blood contains less than 10% of immature white blood cells. The chronic phase is associated with fewer symptoms and a better response to treatment. Nilotinib is a drug that is approved for the treatment of patients with newly diagnosed chronic myeloid leukemia in chronic phase. It is not clear whether changing the dose of nilotinib based on patient response would be more effective.

This study included 421 patients from 18 countries. 77.9% of patients received the full 24 months of treatment. 22.1% of patients stopped treatment early due to reasons such as side effects. The initial dose of nilotinib for all patients was 300 mg twice a day. This could be increased to 400 mg twice a day if the patient was not responding to treatment.

The average dose of nilotinib was 599 mg/day. Overall, 34.2% of patients received a reduced dose of nilotinib at any time during the study. 20.9% of patients had their nilotinib dose increased to 400 mg twice daily due to lack of effectiveness.

The major molecular response refers to a very low level of mutated BCR-ABL protein that is seen in chronic myeloid leukemia. At 12 months, 70.8% of patients had achieved a major molecular response. At 24 months, 81% of patients had achieved a major molecular response. The average time to a major molecular response was 5.8 months.

A complete cytogenetic response means that no abnormal cancer cells were detected through genetic analysis. 58.7% of patients achieved a complete cytogenetic response by 6 months. At 24 months, 74.1% of patients achieved a complete cytogenetic response. At 24 months, 97% of patients were alive without worsening disease.

48.7% of patients had adverse events (undesired effect of treatment) that led to a change in dose of treatment. The most common non-blood related adverse events were headache, rash and nausea. 11.9% of patients had low levels of neutrophils (type of white blood cell), and 10.5% of patients had low levels of platelets (cells involved in blood clotting). 

The authors concluded that treatment with 300 mg of nilotinib twice daily in patients with chronic myeloid leukemia in chronic phase was feasible and beneficial. The study suggested that the dose can be reduced or increased as needed.

This study was funded by Novartis, the manufacturers of nilotinib.