Pokorny Rebecca, Stenehjem David D, Gilreath Jeffrey A
Department of Pharmacy, 20270Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
Department of Pharmacy Practice and Pharmaceutical Sciences, 14713University of Minnesota, College of Pharmacy, Duluth, MN, USA.
J Oncol Pharm Pract. 2022 Jun;28(4):916-923. doi: 10.1177/10781552221077254. Epub 2022 Feb 8.
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.
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.
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.
Future research is warranted to validate these findings and determine the utility of metformin added to TKI therapy.
口服酪氨酸激酶抑制剂（TKIs）是慢性髓性白血病（CML）的一线治疗方法。完全细胞遗传学缓解（CCyR）与总生存期延长相关，然而，仅66%-88%的患者在接受TKI治疗一年后实现CCyR。由于单纯TKI治疗无法清除CML干细胞，因此需要旨在实现更快、更深度缓解的策略来提高长期生存率。二甲双胍是一种广泛用于糖尿病患者的降糖药物，在临床前研究中，已显示其可抑制伊马替尼耐药的CML细胞系（K562R）的细胞活力、诱导凋亡并下调mTORC1信号通路。本研究旨在探讨在CML患者中，TKI治疗联合二甲双胍的效用。
在一所学术医疗中心（犹他州盐湖城）对新诊断的慢性期CML成年患者进行了一项观察性研究，以评估使用或不使用二甲双胍的情况下，TKI治疗实现CCyR的情况。采用描述性分析来描述基线特征以及对TKI治疗的缓解情况。
共评估了59例患者。二甲双胍组100%（5/5）的患者以及非二甲双胍组73.6%（39/54）的患者实现了CCyR。在中位随访34.5个月后，两组中约20%的患者复发（定义为在研究期间失去CCyR）。
有必要开展进一步研究以验证这些发现，并确定TKI治疗联合二甲双胍的效用。
