Flumatinib versus nilotinib as first-line therapy for chronic myeloid leukemia in chronic Phase: A propensity score-matched cohort study

Abstract Background Flumatinib, the first China-developed second-generation tyrosine kinase inhibitor (TKI), shares structural similarities with nilotinib and both demonstrate promising efficacy as first-line treatments for chronic myeloid leukemia (CML). However, current research primarily focuses on individual drug evaluations but lacks direct comparisons between second-generation TKIs as first-line therapy for CML. The present investigation is designed to conduct a comparative assessment of the efficacy and safety characteristics between flumatinib and nilotinib in real-world clinical practice. Method Using multicenter data with propensity score matching, we conducted a comparative analysis of the efficacy (including response rate and progression-free survival) and safety (including adverse events, dose reduction and treatment discontinuation rates) of nilotinib versus flumatinib as first-line treatments for chronic-phase chronic myeloid leukemia (CML-CP) patients. Result The clinical data of 315 newly diagnosed patients with CML-CP who received nilotinib (N=138) or flumatinib (N=177) treatment were analyzed. After propensity score analysis with 1:1 matching, 135 patients were included in each of the nilotinib and flumatinib groups. The median age of both cohorts was 39 years old. There was no significant difference in the baseline. The cumulative incidences of complete cytogenetic response (CCyR), major molecular response (MMR), molecular response 4.0 (MR4.0) and molecular response 4.5 (MR4.5) at 6 months in the nilotinib group and the flumatinib group were 69% and 71%, 30% and 33%, 9% and 10%, 6% and 7%, respectively; the cumulative incidences of CCyR, MMR, MR4.0, and MR4.5 at 12 months were 93% and 95%, 63% and 64%, 47% and 35%, 33% and 28%, respectively; the cumulative incidences of MMR, MR4.0, and MR4.5 at 24 months were 94% and 92%, 68% and 57%, 56% and 48%, respectively. There was no statistically significant difference in the cumulative response rates between the two cohorts (p = 0.8141, p = 0.9027, p = 0.1548, p = 0.2198). Overall, the overall efficacy of flumatinib and nilotinib as first-line treatments for CML-CP is comparable, but there are significant differences in their toxicity profiles. Flumatinib is more likely to cause diarrhea and renal function impairment, while nilotinib is mainly characterized by elevated bilirubin and lipase levels. Conclusion The overall efficacy of flumatinib and nilotinib as first-line therapies for CML-CP is comparable, but there are significant differences in their toxicity profiles.