Found 1 Presentation For Request "31p"
31P - A study to assess the efficacy and feasibility of adding pioglitazone to imatinib in patients of CML with suboptimal response in a resource-limited setting (ID 148)
- Shina Goyal (Bangalore, India)
- Shina Goyal (Bangalore, India)
- Govind Babu (Bengaluru, India)
- Dasappa Lokanatha (BENGALURU, India)
- Jacob A. Linu (Bengaluru, India)
- K. N Lokesh (Bengaluru, India)
- Antapura H. Rudresha (Bangalore, Karnatka, India)
- Lakkavalli K. Rajeev (Bangalore, India)
- Saldanha Smitha (Bengaluru, India)
Abstract
Background
Chronic myeloid leukemia (CML) is characterized by the production of BCR-ABL oncoprotein that has enhanced tyrosine kinase activity. The use of imatinib has redefined the survival of CML patients. Further understanding of disease pathogenesis has led to the identification of quiescent CML Leukemic Stem Cells (LSC) that are resistant to tyrosine kinase inhibitors (TKI) and lead to failure to achieve complete molecular response in many patients. The PPAR-γ agonists can purge them out of quiescence, thereby sensitizing them to imatinib. Hence, combining the two can act in synergy to deplete the leukemic cells. The objective of our study was to determine if the addition of PPAR-γ agonist, pioglitazone to imatinib could attain major molecular response (MMR) in patients who fail to achieve optimal response with imatinib.
Methods
Patients of CML-CP who failed to achieve MMR after at least 12-15 months of treatment with imatinib 400/600 mg and were IRMA negative were included in the study. They were continued on imatinib and received pioglitazone 30 mg once daily for 12 months with monitoring of BCR-ABL transcript levels at 6 and 12 months. Hereby we present the 6-month outcomes of these patients.
Results
A total of 31 patients were included of which 77.4% (n=24) had a decrease in BCR-ABL levels after 6 months with 16 patients (51.6%) showing more than 50% decrease and 7 patients (22.5%) achieving MMR. Two patients discontinued pioglitazone (after 5 and 6 months respectively) due to grade 1 pedal edema. No other patients had any significant increase in weight or a decrease in hemoglobin (p>0.05). There was no episode of hypoglycemia recorded. Patients with high BCR-ABL levels at the start of pioglitazone did not respond well, this could be due to other mechanisms of imatinib resistance.
Conclusion
Preliminary data show that the combination of PPAR-γ agonists with imatinib increases the response rates in CML patients by increasing the sensitivity to imatinib. This requires validation in randomized studies to identify the subgroup of patients who would derive clinical benefit with the addition of pioglitazone. It can be a good option in a low-resource setting where the availability of second-generation TKIs is still limited.
Legal entity responsible for the study
Department of Medical Oncology, Kidwai Memorial Institute of Oncology.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.