Comparative clinical and molecular outcomes of first, second, and third-generation tyrosine kinase inhibitors in chronic myeloid leukemia: A comprehensive Bayesian network meta-analysis.

Abstract

e18566 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 less-explored. As such, we have performed a Bayesian network meta-analysis to evaluate the relative efficacy profiles of these TKIs in treating CML. Methods: A systematic literature search of PubMed, Embase, Cochrane Library, and ClinicalTrials.Gov databases identified clinical trials on effectiveness of different generations of TKIs in CML. A Bayesian network meta-analysis performed in Rstudio pooled percentage (%) mean differences (MD) and risk ratios (RR) with 95% credible intervals using random effects model or fixed effects model based on deviance information criterion (DIC) value. Results: 25 studies involving 12,852 patients were included in our analysis. For (%) major molecular response (MMR) at 12 months, Asciminib showed the highest efficacy (%MD = 27.03, CrI: 7.46–46.44, SUCRA: 82.3), followed by Ponatinib (%MD = 26.86, CrI: -6.1 to 59.72, SUCRA: 74.5) and Nilotinib (%MD = 18.84, CrI: 11.63–25.88, SUCRA: 63.27). Dasatinib (%MD = 16.74, CrI: 7.51–25.47, SUCRA: 54.02) and Bosutinib (%MD = 6.31, CrI: -3.79 to 16.77, SUCRA: 22.72) were less effective. Imatinib, the control drug, had the lowest SUCRA value (3.2). For (%) complete cytogenetic response (CCR) at 12 months, Ponatinib (%MD = 12.54, CrI: -9.33 to 34.33, SUCRA: 73.24) ranked highest, followed by Dasatinib (%MD = 8.76, CrI: -2.60–20.49, SUCRA: 63.48) and Nilotinib (%MD = 7.44, CrI: -2.33 to 17.36, SUCRA: 56.72). Bosutinib (%MD = 5.81, CrI: -7.96 to 20.34, SUCRA: 46.91) and Imatinib (SUCRA: 9.67) ranked lower. For anemia, Nilotinib (RR = 0.61, CrI: 0.37–0.61, SUCRA: 86.43) and Asciminib (RR = 0.64, CrI: 0.31–1.24, SUCRA: 81.13) demonstrated the lowest risk, while Dasatinib (RR = 1.17, CrI: 0.73–1.92, SUCRA: 11.83) had the highest. Conclusions: Our findings demonstrated Asciminib, Ponatinib, and Nilotinib as the most effective TKIs for improving (%) MMR and (%) CCR while minimizing anemia, neutropenia, and thrombocytopenia risks. Dasatinib demonstrated higher toxicity risks, and Imatinib ranked lowest in efficacy and safety, thereby reaffirming the value of newer TKIs in managing CML. Intervention/Outcome(RR, CrI, SUCRA) NeutropeniaIncidence ThrombocytopeniaIncidence Asciminib 0.71(0.51–0.99),44.24 1.28(0.48–3.33), 44.02 Bosutinib 0.52(0.41–0.67), 79.18 1.35(0.66–2.76),36.58 Dasatinib 1.09(0.88–1.36),4.4 1.43(0.73–2.82),31.26 Imatinib (Control, SUCRA) 17.06 67.58 Nilotinib 0.56(0.42–0.64),71.26 0.78(0.39–1.27),89.35 Ponatinib 0.43(0.17–0.98),83.96 1.59(0.39–6.47),31.2