Background <p>Imatinib mesylate is a selective tyrosine kinase inhibitor that has emerged as a prototype for targeted therapy in managing hematologic malignancies. This study aims to evaluate the therapeutic response to imatinib mesylate administered at a daily dosage of 400&#xa0;mg in patients diagnosed with chronic-phase chronic myeloid leukemia (CML) through regular molecular-level monitoring.</p> Methods <p>The study cohort comprised 242 patients diagnosed with CML during the period from January 2015 to December 2019. A total of 1,187 samples were systematically collected at five predetermined intervals: 3–5 months, 6–11 months, 12–17 months, 18–23 months, and ≥ 24 months following the initiation of therapy. Levels of BCR-ABL1^IS transcripts were quantified employing reverse transcription-quantitative polymerase chain reaction (RT-qPCR), with ABL1 as the reference control gene. The results were quantitatively expressed as percentages in accordance with the International Scale (IS).</p> Results <p>Analysis of molecular response profiles for patients from all intervals (<i>n</i> = 69) indicated that 73.9% achieved a reduction of ≥ 1 log in BCR-ABL1^IS transcripts within the first 3–5 months. By the 12–17 month interval, 92.7% exhibited a minimum 1-log reduction, and 72.4% attained a reduction of ≥ 2 logs. In 69 patients with complete monitoring, 92.7% exhibited ≥ 1-log reduction at 12–17 months, and 17.4% had undetectable BCR-ABL1^IS at ≥ 24 months. Among the full cohort (<i>n</i> = 242), 46.8% achieved a molecular response (MMR) by months 12–17.</p> Conclusions <p>The data elucidate that Azerbaijani patients in the chronic phase of CML receiving imatinib at a dosage of 400&#xa0;mg per day demonstrate responses comparable to those observed in randomized international studies, underscoring the significance of regular molecular monitoring.</p>