RESUMO
Several research and market developments in the past 5 years could influence front-line and subsequent-line strategies in chronic myeloid leukaemia. These developments include the increased availability of effective and safe generic imatinib at affordable prices, studies showing that doses of tyrosine kinase inhibitors (TKIs) lower than the approved dose are effective and less toxic, studies showing that dose-adjusted ponatinib therapy at a reduced dose is effective and substantially safer than approved doses, and the approval of asciminib as third-line therapy in 2021. With the availability of an affordable generic imatinib, all patients with chronic myeloid leukaemia globally should be able to access a lifetime supply. The availability of reduced-dose schedules of generic second-generation TKIs, which are less toxic and produce faster deep molecular response than imatinib, might make them more appealing to use as front-line therapy. In the subsequent-line setting, the role of different TKIs as second, third, and later lines of therapy depends on the evolving front-line use. Dose-adjusted ponatinib schedules have shown better efficacy and safety with long-term follow-up. Ponatinib is the favoured therapy for patients with second-generation-TKI resistance or chronic myeloid leukaemia with 944CâT (Thr315Ile)-mutated BCR-ABL1. Studies of asciminib are needed in larger numbers of patients and with longer follow-up than has been done previously to better assess its comparative efficacy, safety, and survival data (vs ponatinib). The role of third-generation TKIs as second-line therapy following front-line resistance to second-generation TKIs needs to be evaluated. New and mature data with TKI therapy in chronic myeloid leukaemia are producing observations that encourage continuous discussion of the optimal treatment recommendations and frameworks in chronic myeloid leukaemia.