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Can Combining These Two Drugs Safely Improve CML Response?


December 29, 2016

In a study published in Cancer, a team of French researchers suggest that pioglitazone in combination with imatinib may safely improve outcomes for patients with chronic myeloid leukemia (CML).

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After finding that peroxisome proliferator-activated receptor γ agonists target chronic myeloid leukemia (CML) quiescent stem cells, investigators led by Phillippe Rousselot, MD, PhD, Université Versailles Saint-Quentin-en-Yvelines, Université Paris Saclay (Le Chesnay, France), conducted a clinical trial assessing whether pioglitazone add-on therapy to imatinib could impact CML residual disease.

For the trial, they enrolled patients with CML who had received imatinib for at least 2 years at a stable daily dose. These patients were then given pioglitazone at a dosage of 30 to 45 mg/day in addition to regularly scheduled imatinib. The primary endpoint of the study was incidence of progression from major molecular response (MMR) to molecular response 4.5 (MR4.5) during a 12-month period.

A total of 24 patients were included in the study and administered both drugs. No pharmacological interactions were observed, but half of the patients (n=12) experienced weight gain and a mean decrease of .4 g/dL in hemoglobin concentration. Cumulative incidence of MR4.5 was 56% by 12 months, though there was considerable variance in duration. Still, 88% of 17 evaluable patients who were still on imatinib at 48 months achieved MR4.5.

Investigators estimated that incidence of progression from MMR to MR4.5 over 12 months was 23% in a parallel cohort of patients who received only imatinib.

Thus, they concluded that a combination regimen of imatinib and pioglitazone could safely improve response in patients with CML. However, they added that the results will need to be proved within a randomized clinical trial. 

Reference

Rousselot P, Prost S, Guilhot J, et al. Pioglitazone together with imatinib in chronic myeloid leukemia: A proof of concept study [Published online ahead of print December 27, 2016]. Cancer. doi 10.1002/cncr.30490.

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