Reasons of treatment switching from first generation to second and third generations of TKIs among CML patients in Iraq -Kurdistan region from 2014-2024

Abstract

Background: Chronic myeloid leukemia (CML), is one of the myeloproliferative disorders with a characteristic cytogenetic abnormality resulting in the BCR-ABL fusion gene. Imatinib Mesylate is an effective agent for treating patients in all stages of CML. Imatinib directly inhibits the constitutive tyrosine kinase activity. Imatinib binds to BCR-ABL kinase domain by preventing the transfer of a phosphate group to tyrosine on the protein substrate and the subsequent activation of phosphorylated protein.

Materials and Methods: This cross-sectional study included 90 CML patients at the outpatient clinic of a reference hospital in the Kurdistan Region of Iraq, between 2014 and 2024. The questionnaire was divided into two categories: the first part comprised patients’ demographic characteristics, which include sex, age, residency, and chronic disease at time of diagnosis (D.M., HTN, hypothyroidism, asthma, and IHD). The second part consisted of duration of exposure to imatinib, clinical adverse effects at the time of switching, blood characteristics, renal function tests (RFT), liver function tests (LFT), quantitative PCR at the time of switching, and the reason for switching.

Results: This study show the outstanding effectiveness of imatinib was highest in 11-20 months which was 41(45.56%), followed by 1-10 months 19(21.11%) and the lowest rates was found in 31-40 months which was 8(8.89%). The most frequent imatinib-related AEs (any grade) occurring in 45% of total patients were Diarrhea 10(11.11%), Myalgia 7(7.78%), Epigastric pain 5(5.56%), Multiple skin lesion 4(4.44%) and Fatigue 2(2.22%). Furthermore, the effect of long term TKI treatment on kidney function and the incidence and prognosis of chronic kidney disease (CKD) in CML patients, 86 (95.56%) has normal renal function tests (RFT) an only 4(4.44%) has increasing urea and creatinine. On the other hand, 83 (92.22%) has normal liver function tests and only 1 (1.11%) has elevated total bilirubin, 1(1.11%) increasing 1fold, 4(4.44%) patients increasing 2folds and 1(1.11%) increasing 3folds.

Conclusion: In this study imatinib showed superior efficacy and a favorable safety profile in patients with newly diagnosed chronic-phase CML. Furthermore, TKI intolerance should not be called failure anymore; it encourages an immediate change of TKI therapy. Failure refers to situations where physicians or patients switched TKIs due to toxicities, believing that reducing the dose would compromise treatment effectiveness.