Comparative effectiveness of first, second, and third-generation tyrosine kinase inhibitors in chronic myeloid leukemia: A systematic review and frequentist network meta-analysis.

Abstract

e18564 Background: Tyrosine kinase inhibitors (TKIs) are highly effective for chronic myeloid leukemia (CML) carrying the BCR-ABL fusion gene. The advent of first-generation TKIs, Imatinib, and the newer second or third-generation TKIs completely changed the CML landscape. Yet their relative efficacy remains unclear. As such, we have performed a systematic review and network meta-analysis (NMA) of the relative efficacy profiles of these TKIs in treating CML. Methods: This network meta-analysis was performed according to the PRISMA guidelines. We searched for relevant articles in PubMed, Embase, Cochrane Library Databases, and ClinicalTrials.Gov for studies assessing first-, second-, and third-generation TKIs. Search terms included combinations of "Imatinib," "Dasatinib," "Nilotinib," "Bosutinib," "Ponatinib," and "Asciminib," along with "Chronic Myeloid Leukemia." A total of 176 studies were identified, with the inclusion criteria being met by 25 trials included after screening. We used the Frequentist method with the Netmeta package in R Studio for statistical analysis. The outcomes estimates were presented as mean differences (MD) with 95% confidence intervals for continuous data and in a random-effects model. Results: Our primary outcome in this network meta-analysis was the major molecular response (MMR) at 12 months between Imatinib and other Tyrosine kinase inhibitors. Results were given in terms of efficacy. Asciminib demonstrated the most significant improvement, with a mean difference (MD) of 22.45% (95% CI: 15.84 to 29.07; z = 6.65, p < 0.0001), indicating a robust molecular response relative to Imatinib. Bosutinib also showed a notable positive effect, with an MD of 10.71% (95% CI: 4.49 to 16.92; z = 3.38, p = 0.0007). Dasatinib exhibited an MD of 7.32% (95% CI: 4.98 to 9.67; z = 6.12, p < 0.0001), further supporting its efficacy compared to Imatinib. Nilotinib showed an MD of 12.48% (95% CI: 5.05 to 19.92; z = 3.29, p = 0.001), while Ponatinib demonstrated a more variable response with an MD of 42.00% (95% CI: -44.41 to 128.41; z = 0.95, p = 0.3408), though this result was not statistically significant. These findings suggest that newer-generation TKIs, particularly Asciminib and Bosutinib, may offer superior molecular responses in treating chronic myeloid leukemia compared to Imatinib. Conclusions: This network meta-analysis highlights the superior efficacy of newer-generation TKIs, particularly Asciminib and Bosutinib, in achieving major molecular response at 12 months compared to Imatinib in chronic myeloid leukemia. These findings support the potential of second-and third-generation TKIs as more effective treatment options for CML.