TAT 2020: Adding Diabetes Drug to Imatinib Therapy for CML
Posted: Monday, March 23, 2020
Adding the diabetes drug pioglitazone to imatinib therapy may increase response rates in patients with chronic myeloid leukemia (CML) by increasing sensitivity to imatinib, according to preliminary data originally intended to be presented at the European Society for Medical Oncology (ESMO) Targeted Anticancer Therapies (TAT) Congress 2020 in Paris (Abstract 31P). Although these data require validation in randomized studies, “it may be a good option in a low-resource setting, where the availability of second-generation [tyrosine kinase inhibitors] is still limited,” explained Shina Goyal, MD, of the Kidwai Memorial Institute of Oncology, Bangalore, India, and colleagues.
Pioglitazone, a peroxisome proliferator-activated type gamma receptor (PPAR-γ) agonist that is therapeutically used to combat hyperglycemia associated with type 2 diabetes, can reportedly “purge” CML leukemic stem cells out of quiescence, thus sensitizing them to imatinib. This study included 31 patients with CML in chronic phase who did not achieve a major molecular response after at least 12 to 15 months of treatment with imatinib. Patients continued imatinib and received pioglitazone at 30 mg once daily.
A total of 24 patients (77.4%) experienced a decrease in BCR-ABL levels after 6 months. Approximately half of the study patients (n = 16) had a greater than a 50% reduction in BCR-ABL levels, and seven patients (22.5%) achieved a major molecular response. Those with high BCR-ABL levels when pioglitazone therapy was initiated did not respond well, possibly due to other mechanisms of imatinib resistance.
As for safety, two patients discontinued pioglitazone due to grade 1 pedal edema after 5 and 6 months, respectively. No other patients had any significant increase in weight or a decrease in hemoglobin, and no episodes of hypoglycemia were recorded.
Disclosure: The study authors reported no conflicts of interest.