Potential drug-drug interactions and their effects on TKI responses and toxicities in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors (TKIs)

Introduction: This study aimed to evaluate potential drug-drug interactions from systemic medications in CML patients treated with TKIs, and their impact on clinical, laboratory, and molecular outcomes. Method: A retrospective analysis was performed on data from 172 CML patients followed at Istanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine between May 2003 and April 2025. Clinical and laboratory data at diagnosis and at months 3, 6, 9, and 12 before and after the addition of concomitant drugs were analyzed using rank-based ANCOVA. Adverse events and laboratory changes after additional medications were thoroughly recorded. Results: The mean age was 48.9±15.2 years, and 50.6% of the patients were female. Imatinib was the most frequently used TKI (82.6%). Comorbidities were present in 51.7% of patients. The rates of polypharmacy and PPI use were 29.7% and 28.5%, respectively. Most adverse effects were mild (57.6%), with myalgia (12.2%) being the most common. Significant hematologic improvement was observed by month 3 (p<0.001). At this time, 45.4% had not achieved MMR, while 38.2% had DMR. The rate of undetectable molecular disease was higher in late versus early additional drug users (46.4% vs 28.4%, p<0.001). Polypharmacy was associated with significantly lower DMR from month 6 onward (p=0.047). PPI use had no significant impact on molecular response during follow-up (p=NS). Conclusion: In CML patients, systematic assessment of drug interactions and personalized treatment strategies may not only improve molecular response but also positively influence survival. Keywords: Chronic Myeloid Leukemia (CML), Tyrosine Kinase Inhibitors (TKIs), drug-drug interactions, BCR::ABL1