Comparative Efficacy and Safety of New-Generation Tyrosine Kinase Inhibitors in Achieving Deep Molecular Remission and Remission Without Treatment in Chronic Myeloid Leukemia

Chronic myeloid leukemia (CML) is a model disease in which the emergence of tyrosine kinase inhibitors (TKIs) has radically changed the natural course and prognosis, transforming a once fatal pathology into a chronically controlled condition. However, the escalation of therapeutic goals — from cytogenetic remission to deep molecular response (DMR) and, ultimately, treatment-free remission (TFR) — has highlighted the need for highly active yet safe drugs. The modern arsenal of the latest second- and third-generation ITKs and the allosteric inhibitor asciminib opens up fundamentally new possibilities, but also poses the question of optimal choice for clinicians in terms of efficacy, toxicity, and resistance.A literature review was conducted to summarize the comparative analysis of the efficacy and safety of second- and third-generation TKIs and asciminib.Asciminib radically changes the therapeutic landscape of CML. In clinical trials, it significantly outperforms all existing first-line treatment regimens, including second-generation TKIs, in terms of the frequency of major and deep molecular responses (MMR, DMR), while demonstrating a more favorable safety profile. This refutes the traditional “efficacy versus toxicity” trade-off and provides grounds for considering the drug as a likely new first-line standard for most patients with newly diagnosed CML-CP. Rapid and sustained induction of deep responses with a lower incidence of adverse events potentially increases the number of patients who can achieve treatment-free remission (TFR).Ponatinib remains a key agent in cases of high-level resistance. As the most potent ATP-competitive inhibitor, it is particularly important for patients with the T315I mutation or complex mutations. The introduction of an adaptive dosing regimen in the OPTIC study has maintained high efficacy while significantly reducing the risk of arterial occlusive complications. The choice between ponatinib and asciminib in the third line is a practical example of personalized medicine, where decisions are based on the mutation profile, comorbidity, and individual therapeutic goals of the patient.The combined or sequential use of pharmacodynamically complementary agents (asiminib with ATP-competitive TKI) may be a way to overcome the most persistent forms of resistance and, possibly, to eliminate leukemic stem cells, bringing TFR closer to a wider range of patients.