Adding Pioglitazone to Imatinib May Improve Response in CML

Share this content:
STAT5 plays a key role in many hematologic malignancies.
STAT5 plays a key role in many hematologic malignancies.

In patients with chronic myeloid leukemia in chronic phase (CML-CP), pioglitazone in combination with imatinib was well tolerated and was associated with a favorable response rate, suggesting that adding pioglitazone to a kinase inhibitor may have a synergistic effect.1

The proof-of-concept phase 2 ACTIM study ( Identifier: NCT02888964), published in the journal Cancer, showed that 56% (95% CI, 37-76) of 24 patients with CML-CP who were treated with imatinib plus pioglitazone achieved a molecular response 4.5, defined BCR-ABL1/ABL1IS RNA levels of 0.0032% or less, by month 12.

In addition, 88% of 17 evaluable patients who were still receiving imatinib reached molecular response 4.5 by month 48. Therapy duration ranged from 1.9 to 15.5 months.

In comparison, investigators estimated in a parallel cohort of patients treated with imatinib alone that 23% would spontaneously convert from major molecular response to molecular response 4.5.

For the study, patients with CML-CP who had been treated with imatinib for at least 2 years at a stable daily dose and achieved a major molecular response but not a molecular response 4.5 were eligible for enrollment. In addition to imatinib, patients received pioglitazone starting at a dose of 30 to 45 mg per day.

Pioglitazone, a hypoglycemic agent used to treat diabetes mellitus type 2, is an agonist of peroxisome proliferator-activated receptor γ (PPAR-γ), which have been shown to decrease transcription of STAT5. STAT5 is a transcription factor that plays a key role in many hematologic malignancies.

Investigators are enrolling patients for the ACTIW randomized trial ( Identifier: NCT02767063) to evaluate the optimal duration of imatinib with pioglitazone and determine the ideal PPAR-γ agonist to be used in this setting.


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

You must be a registered member of ONA to post a comment.

Sign Up for Free e-newsletters

Regimen and Drug Listings


Bone Cancer Regimens Drugs
Brain Cancer Regimens Drugs
Breast Cancer Regimens Drugs
Endocrine Cancer Regimens Drugs
Gastrointestinal Cancer Regimens Drugs
Genitourinary Cancer Regimens Drugs
Gynecologic Cancer Regimens Drugs
Head and Neck Cancer Regimens Drugs
Hematologic Cancer Regimens Drugs
Lung Cancer Regimens Drugs
Other Cancers Regimens
Rare Cancers Regimens
Skin Cancer Regimens Drugs