Adding pioglitazone to imatinib in chronic myeloid leukemia

This paper studied the use of pioglitazone (Actos) with imatinib (Gleevec) in patients with chronic myeloid leukemia (CML). The authors concluded that the addition of pioglitazone improved response. 

Chronic myeloid leukemia is a cancer of the bone marrow, where there is an excess of white blood cells. It is strongly associated with a genetic abnormality of the Philadelphia chromosome 22. The abnormal gene is known as BCR-ABL1. Drugs such as imatinib target the BCR-ABL1 gene.

Residual disease occurs when cancer cells remain during and after treatment, even when there are no symptoms. The presence of residual disease can be measured through levels of BCR-ABL1 gene. Pioglitazone is a treatment for type 2 diabetes. It is suggested that pioglitazone can target these residual cancer cells to better respond to imatinib treatment. 

24 patients with chronic myeloid leukemia with more than 2 years of imatinib therapy were studied. These patients had a major molecular response to imatinib. This meant that the ratio of BCR-ABL1/ABL1 (the ratio of abnormal to normal genes) was less than 0.1%. These patients continued to receive imatinib with the addition of pioglitazone over 1 year. A molecular response was measured after 1 year. This was defined as the ratio of BCR-ABL1/ABL1 of less than 0.0032%.

56% of patients achieved a molecular response over the course of 12 months. At 12 months, 29.1% of these patients remained in molecular response.

23 patients were followed-up for 48 months in total. Of these, 58.3% remained in molecular response at 48 months. Of the 17 patients who remained on imatinib and were not switched to another drug, 88.2% reached molecular response by 48 months.

For comparison, a similar group of patients who received imatinib alone were studied. It was estimated that 23% of patients on imatinib alone converted from major molecular response to molecular response over 12 months.

There was an overall average 0.4 g/dL decrease in hemoglobin concentration (measure of red blood cell level). Weight gain was experienced by 12 patients. There were no cases of bladder cancer. 

The authors concluded that the use of pioglitazone with imatinib improved rates of molecular response in chronic myeloid leukemia. 

This study included a small number of patients, and did not directly compare patients treated with and without pioglitazone. Further large scale trials are needed.