Impact of Metformin on Tyrosine Kinase Inhibitor Response in Chronic Myeloid Leukemia

Objective: Oral tyrosine kinase inhibitors (TKIs) are first line therapy for chronic myeloid leukemia (CML). A complete cytogenetic response (CCyR) correlates with increased overall survival, however only 66%-88% of patients achieve CCyR after one year of TKI treatment. Because TKI therapy alone cannot eliminate CML stem cells, strategies aimed at achieving faster and deeper responses are needed to improve long-term survival. Metformin is a widely prescribed glucose-lowering agent for patients with diabetes and in preclinical studies, has been shown to suppress cell viability, induce apoptosis, and downregulate the mTORC1 signaling pathway in imatinib resistant CML cell lines (K562R). This study aims to investigate the utility of metformin added to TKI therapy in patients with CML.

Data Sources: An observational study at an academic medical center (Salt Lake City, UT) was performed for adults with newly diagnosed, chronic-phase CML to evaluate attainment of CCyR from TKI therapy with or without concomitant metformin use. Descriptive analyses were used to describe baseline characteristics and attainment of response to TKI therapy.

Data Summary: Fifty-nine patients were evaluated. One hundred percent (5 of 5) in the metformin group and 73.6% (39 of 54) in the non-metformin group achieved CCyR. Approximately 20% of patients in both groups relapsed (defined by a loss of CCyR during study) after a median 34.5 months of follow-up.

Conclusions: Future research is warranted to validate these findings and determine the utility of metformin added to TKI therapy.