Comparing tyrosine kinase inhibitors: Patients more likely to achieve molecular response with nilotinib than with imatinib

This study compared the effectiveness of two types of tyrosine kinase inhibitors – imatinib (Gleevac) and nilotinib (Tasigna) – for chronic myeloid leukemia (CML). Researchers reported higher treatment response rates (on a molecular level) with nilotinib than with imatinib. No differences were observed between different doses of nilotinib.

Most patients with CML have an abnormally short chromosome (cell structure that carries genetic information) called the Philadelphia chromosome. This chromosome carries a gene abnormality called BCR-ABL, which plays a role in the development of CML.

Patients treated for CML who are no longer showing any cells with the Philadelphia chromosome in their blood or bone marrow are considered to have reached complete cytogenetic response. An even stronger response to treatment is molecular response, when the amount of BCR-ABL gene in the blood is low or untraceable. Major molecular response is typically the ultimate goal of CML treatment.

Tyrosine kinase inhibitors are a type of targeted therapy that block enzymes called tyrosine kinases and are a first-line treatment for CML. Imatinib is the most commonly used tyrosine kinase inhibitor. However, it has been suggested that second-generation tyrosine kinase inhibitors, such as nilotinib, could be more effective.

The aim of this study was to compare treatment response rates between imatinib and nilotinib.

846 patients with chronic (early) phase CML who were positive for the Philadelphia chromosome were included in this study. Patients were randomly assigned to either treatment with imatinib (at 400 mg per day) or with nilotinib (at either 300 or 400 mg twice per day). Molecular response rates at 12 months were compared between treatment groups.

Major molecular response rates at 12 months were significantly higher for patients treated with lower (44%) or higher dose of nilotinib (43%) than those treated with imatinib (22%). The average time to major molecular response was also significantly shorter for patients treated with nilotinib (8.6 to 11 months) compared to imatinib (longer than 12 months). The rates of complete cytogenetic response by 12 months were 80% for low-dose nilotinib and 78% for high-dose nilotinib. These were significantly higher compared to imatinib (65%).

4% of patients receiving imatinib progressed to more advanced CML during the study period. This was significantly higher compared to the two nilotinib groups (both less than 1%). However, no patient who had reached major molecular response progressed to advanced CML.

Nilotinib and imatinib were both associated with good safety. Side effects related to the stomach or intestines as well as fluid retention were more common among patients receiving imatinib. Skin-related side effects and headaches were more common among those receiving nilotinib. Serious side effects were uncommon across all treatment groups.

Researchers concluded that patients treated with nilotinib were more likely to achieve molecular response than those treated with imatinib.

Researchers reported superior treatment response rates (on a molecular level) with nilotinib than with imatinib.

This study had a relatively short follow-up.