Navigating the Management of Chronic Phase CML in the Era of Generic BCR::ABL1 Tyrosine Kinase Inhibitors

Abstract

Over the past several years, advances in research, treatment, and market dynamics have impacted treatment strategies in chronic myeloid leukemia in chronic phase (CML-CP). They include the broader availability of cost-effective generic imatinib, and soon other generic second-generation tyrosine kinase inhibitors (TKIs). Access to affordable generics means that all patients with CML-CP should have access to safe and highly effective lifelong therapies. When overall survival is the treatment endpoint, imatinib provides a good treatment value. Second-generation TKIs may be the best frontline strategy when treatment-free remission is the goal. Recent studies have shown maintained efficacy and reduced toxicity when TKIs are used at reduced dosing. Reduced-dose schedules of second-generation TKIs (which are less toxic and induce faster deep molecular responses) may render generic second-generation TKIs a more attractive treatment option. Adjusting the dose of TKI in the presence of mild-to-moderate, or even severe but reversible, adverse events may be preferable to switching to a different TKI. The selection of second-line and beyond therapies depends on the evolving patterns observed with frontline treatment. Dose-adjusted ponatinib schedules have demonstrated improved efficacy and safety in patients resistant to second-generation TKIs or those with T315I-mutated disease. For asciminib, longer-term follow-up is needed to better evaluate its safety and efficacy compared with ponatinib. Allogeneic stem cell transplantation represents a valid alternative to newer-generation TKIs, with a better treatment value when TKIs are priced at >$40,000/year.