Modeling Treatment-Free Remission Outcomes for Asciminib in Newly Diagnosed Chronic Myeloid Leukemia: Assumptions, Methodology, and Projections
Author(s)
David Cendoya Revuelta, MSc1, Victor Genestier, MSc2, Shaun Walsh, MSc3, Isabelle Lundqvist, MSc4, Vladimir Babiy, PharmD, PhD5, Pranay Kassi, MSc6, Abhay Choubey, MBA6.
1Amaris Consulting, Barcelona, Spain, 2Amaris Consulting, Toronto, ON, Canada, 3Novartis Ireland Ltd, Dublin, Ireland, 4Novartis Sverige AB, Kista, Sweden, 5Novartis Pharmaceuticals UK Ltd, London, United Kingdom, 6Novartis Healthcare Pvt. Ltd., Hyderabad, India.
1Amaris Consulting, Barcelona, Spain, 2Amaris Consulting, Toronto, ON, Canada, 3Novartis Ireland Ltd, Dublin, Ireland, 4Novartis Sverige AB, Kista, Sweden, 5Novartis Pharmaceuticals UK Ltd, London, United Kingdom, 6Novartis Healthcare Pvt. Ltd., Hyderabad, India.
OBJECTIVES: Treatment-free remission (TFR) is one of the key therapeutic goals in chronic myeloid leukaemia (CML), achievable in patients who sustain a deep molecular response (DMR). Asciminib, a first-in-class BCR::ABL1 inhibitor, demonstrated superior outcomes in the ASC4FIRST trial compared to investigator-selected tyrosine kinase inhibitors (IS-TKIs), achieving higher major molecular response (MMR) rates at 96 weeks (74.1% vs. 52.0%, p < .001) and improved MR4.5 rates ((30.8% vs. 17.6%, p < .005 (unadjusted p-value)).
METHODS: A Markov-based model was developed using a 40 year time horizon to project long-term outcomes of asciminib versus IS-TKIs, including eligibility for TFR. Modelling of TFR focused on patients who had received first-line TKI therapy for at least five years and achieved sustained MR4.5 for a minimum of two years, aligning with European LeukemiaNet guidelines. The eligibility thresholds of five-year treatment duration and DMR—often set at MR4.0—were considered conservative assumptions compared to real-world clinical practice, according to a panel of experts.
RESULTS: Patients enter the model in the Frontline Chronic-Phase Treated health state. Those who respond to treatment can transition through MMR and MR4.5 health states to a dedicated TFR health state. A tunnel-state approach is used to ensure patients meet the TFR eligibility before entering. Transition probabilities were primarily informed by ASC4FIRST data at 96 weeks. At the first eligibility point (5 years), 37.2% of asciminib-treated patients were projected to qualify for TFR, compared to 19.9% for IS-TKIs. Over a 40-year horizon, asciminib increased the probability of achieving TFR by 20.2 percentage points. The projections for IS-TKIs align with TKI long-term clinical trial data.
CONCLUSIONS: The proposed model shows that asciminib can noticeably improve the probability of TFR. Given that TFR reduces medication burden and eliminates tolerability issues, significantly improving quality of life while offering substantial cost savings from discontinued TKI therapy, its inclusion in pharmacoeconomic analysis is essential.
METHODS: A Markov-based model was developed using a 40 year time horizon to project long-term outcomes of asciminib versus IS-TKIs, including eligibility for TFR. Modelling of TFR focused on patients who had received first-line TKI therapy for at least five years and achieved sustained MR4.5 for a minimum of two years, aligning with European LeukemiaNet guidelines. The eligibility thresholds of five-year treatment duration and DMR—often set at MR4.0—were considered conservative assumptions compared to real-world clinical practice, according to a panel of experts.
RESULTS: Patients enter the model in the Frontline Chronic-Phase Treated health state. Those who respond to treatment can transition through MMR and MR4.5 health states to a dedicated TFR health state. A tunnel-state approach is used to ensure patients meet the TFR eligibility before entering. Transition probabilities were primarily informed by ASC4FIRST data at 96 weeks. At the first eligibility point (5 years), 37.2% of asciminib-treated patients were projected to qualify for TFR, compared to 19.9% for IS-TKIs. Over a 40-year horizon, asciminib increased the probability of achieving TFR by 20.2 percentage points. The projections for IS-TKIs align with TKI long-term clinical trial data.
CONCLUSIONS: The proposed model shows that asciminib can noticeably improve the probability of TFR. Given that TFR reduces medication burden and eliminates tolerability issues, significantly improving quality of life while offering substantial cost savings from discontinued TKI therapy, its inclusion in pharmacoeconomic analysis is essential.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
EE590
Topic
Economic Evaluation, Methodological & Statistical Research, Study Approaches
Topic Subcategory
Cost/Cost of Illness/Resource Use Studies
Disease
Oncology, Rare & Orphan Diseases, Systemic Disorders/Conditions (Anesthesia, Auto-Immune Disorders (n.e.c.), Hematological Disorders (non-oncologic), Pain)