What is the optimal dose of imatinib in newly diagnosed chronic myeloid leukemia?

This study explored whether a higher starting dose of imatinib (Gleevac) is safe and effective as a first-line treatment for chronic myeloid leukemia (CML). This study concluded that response rates were similar between the higher and lower dose after 1 year, but the response occurred earlier with the higher dose.

Imatinib is the standard first-line treatment for CML. Imatinib is a tyrosine kinase inhibitor (TKI). TKIs block a protein involved in cancer cell growth and spread. This treatment leads to a cytogenic response (CCyR, a disappearance of the Philadelphia chromosome, the cause of CML) in 82% of patients. The standard starting dose is 400 mg in patients with chronic CML. Previous studies have suggested that a higher dose may lead to higher response rates and a faster time to response.

The study compared the safety and effectiveness of two different starting doses of imatinib. 476 patients were randomly assigned to treatment with 400 mg of imatinib (157 patients) or 800 mg (310 patients). Patients were followed for an average of 17 months. The rate of major molecular response (MMR; decrease in BCR-ABL levels, the abnormal gene present on the Philadelphia chromosome) was measured at 12 weeks.

The rates of CCyR and MMR were not significantly different at 12 months. MMR occurred faster in patients treated with 800 mg. MMR rates were higher in these patients at 3 and 6 months than in patients treated with 400 mg. CCyR occurred in 57% of patients treated with 800 mg at 6 months compared to 45% of patients treated with 400 mg.

Negative side effects occurred more often in patients treated with 800 mg. The most common severe side effects were low levels of neutrophils (white blood cells) in 28.5%, and low platelet levels (blood cells involved in clotting) in 18%. Other negative effects included rash, swelling, and gastrointestinal problems.

This study concluded that response rates were similar between doses of imatinib at 12 months, but responses occurred earlier with a higher dose.