Decision‐Making on First‐Line Treatment Alternatives in Chronic Lymphocytic Leukemia: A Multi‐Criteria Decision Analysis to Elicit Stakeholders' Preferences in Italy

ABSTRACT

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in Western countries. The introduction of targeted therapies has expanded first‐line treatment options, which differ across multiple relevant dimensions, making therapeutic decisions increasingly challenging. A multi‐criteria decision analysis (MCDA) was conducted to identify and quantify the importance of key treatment selection criteria and to evaluate available first‐line alternatives for patients with mutated and unmutated immunoglobulin heavy‐chain variable region (IGHV ^mut /IGHV ^unmut ) gene status, from the perspective of clinicians, patients, payers, and methodologists. The analysis focused on targeted therapies recommended by European Society for Medical Oncology (ESMO) guidelines and reimbursed in Italy, including ibrutinib, acalabrutinib, zanubrutinib, venetoclax + ibrutinib, and venetoclax+obinutuzumab. The MCDA was developed in accordance with International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Good Practice recommendations, using the MACBETH (Measuring Attractiveness by a Categorical‐Based Evaluation Technique) method to elicit stakeholder preferences. Decision criteria were selected based on literature review, stakeholder input, and data availability. Preferences were collected from 20 stakeholders (nine clinicians, five patients, six payers/methodologists) via structured questionnaires. Six criteria were selected: efficacy, safety, quality of life (QoL), drug cost, convenience of administration, and treatment duration. Efficacy and safety emerged among the most important criteria across all groups, with efficacy particularly prioritized in the IGHV ^unmut population. Among the other criteria, notable differences emerged between stakeholder groups: clinicians assigned relatively greater importance to treatment duration, especially in the IGHV ^mut population; patients prioritized QoL more than other groups; payers and methodologists gave more weight to drug cost than clinicians and patients. In the IGHV ^mut population, venetoclax + ibrutinib, and zanubrutinib were the most valued options. In the IGHV ^unmut population, second‐generation Bruton tyrosine kinase inhibitors (zanubrutinib and acalabrutinib) ranked highest. Sensitivity analyses confirmed the robustness of these findings. This is the first MCDA study applied to CLL treatment in Italy. It highlights the value of structured, stakeholder‐informed approaches in supporting value‐based treatment decisions.