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Are Genetic Variants and Plasma Imatinib Levels Linked to Improved Outcomes in CML?

By: Kayci Reyer
Posted: Monday, January 11, 2021

According to research published in Scientific Reports, factors such as steady-state plasma imatinib levels, MDR1 polymorphism, and ABC transporter expression may impact failure-free survival outcomes in patients with chronic-phase chronic myeloid leukemia (CML). Improved survival outcomes seem to be associated with achievement of early molecular response, which appears to be influenced by such factors.

“This study suggests the incorporation of these variables into the imatinib dosing algorithm as predictive biomarkers of response to imatinib therapy,” concluded Poonkuzhali Balasubramanian, PhD, of Christian Medical College, India, and colleagues.

The study included 160 imatinib-naive patients, 108 of whom were male, who had been diagnosed with chronic-phase CML at Christian Medical College. All patients underwent analysis of genetic variants and gene expression as well as day 29 plasma imatinib levels. Sokal scores were low/intermediate for most patients (n = 110), and failure-free survival at 2 years was better for patients with low/intermediate Sokal scores than for those with high Sokal scores (P = .02).

Clinical and survival outcomes were better for patients with ABCB1-C1236T variants, including high day 29 plasma imatinib levels (P = .005), increased rates of early molecular response at 3 months (P = .044), and superior 2-year failure-free survival (P = .003), versus patients with a wild-type genotype. Intracellular imatinib levels were substantially higher for patients with lower ABCB1 mRNA expression (P = .029). Failure-free survival was superior among patients who had achieved early molecular response at 3 or 6 months or major molecular response at 12 months. Among those with higher day 29 plasma imatinib levels, achievement of early molecular response at 3 months (P = .022) and major molecular response at 12 months (P = .041) was more common, resulting in improved failure-free survival at 2 years (P = .05).

Disclosure: The study authors reported no conflicts of interest.



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