SOHO State of the Art Updates and Next Questions | Choosing the Best Frontline BCR::ABL1 Tyrosine Kinase Inhibitor in Chronic Myeloid Leukemia—How to Define the Treatment Value?

Over the last 2 decades, progress in research, treatment approaches, and market dynamics have influenced our treatment of chronic myeloid leukemia in chronic phase (CML-CP). The choice of frontline therapy depends on the treatment goal (normalizing survival only or achieving a treatment-free remission [TFR]), the toxicity profile of each BCR::ABL1 tyrosine kinase inhibitor (TKI), the patient's comorbidities, and the cost and affordability of the treatment. When overall survival is the aim of therapy, generics of imatinib and of second-generation BCR::ABL1 TKIs offer an excellent treatment value. For patients with high-risk CML-CP or those aiming for TFR, second-generation TKIs might be the optimal frontline strategy. Challenges persist in ensuring universal access to therapy, particularly for patients in poorer conditions or geographies. With cost-effective generics now accessible, all patients with CML-CP should have the opportunity to receive imatinib (price < $1000/year worldwide), and most can have access to safe and effective second-generation TKIs. This still may not be possible in the United States and in other nations where second-generation TKIs, even generics, are still too expensive and of poor “treatment value.” Strategies such as dose optimization can enhance the TKI affordability without compromising efficacy, particularly for elderly or low-risk patients. For a novel TKI to become established frontline therapy, it should improve the durable deep molecular response rate (BCR::ABL1 transcripts on the International Scale < 0.01% for ≥ 2 years), demonstrate a favorable safety profile, and provide a good treatment value (cost versus efficacy and safety benefits).