Cost-utility analysis of venetoclax in combination with obinutuzumab as first-line treatment of chronic lymphocytic leukaemia in Spain

Objective: Venetoclax in combination with obinutuzumab has significantly improved efficacy versus immunochemotherapy (progression-free survival) in patients with chronic lymphocytic leukaemia who have not received prior treatment. The objective of this study was to evaluate its efficiency in Spain using a cost-utility analysis. Method: Using a partitioned-survival analysis model adapted to the Spanish context and based on three health states (progression-free survival, survival after progression, and death), a simulation of the evolution of patients who were candidates for initiating first-line treatment was conducted for a lifetime time horizon. Venetoclax in combination with obinutuzumab was compared to the most commonly used therapeutic options for these patients at the time of study design: chlorambucil in combination with obinutuzumab, ibrutinib, fludarabine in combination with cyclophosphamide and rituximab, and bendamustine in combination with rituximab. In order to estimate survival curves, efficacy data were derived from the CLL14 trial and a network meta-analysis. The analysis was conducted from the perspective of the Spanish National Healthcare System and included direct healthcare costs (i.e. pharma-cological costs and their administration), and those associated with the management of the disease and adverse events. The resource use was validated by an expert group. Quality of life data were used to estimate the quality-adjusted life years obtained for each alternative. A threshold of euro 25,000/quality-adjusted life years was used. The robustness of the model was evaluated using deterministic and probabilistic sensitivity analyses. Results: Venetoclax in combination with obinutuzumab was shown to be a dominant alternative compared to the rest of the treatment alternati-ves, with a lower cost per patient (euro -67,869 compared to chlorambucil in combination with obinutuzumab, euro -375,952 compared to ibrutinib, euro -61,996 compared to fludarabine in combination with cyclophospha-mide and rituximab, and euro -77,398 compared to bendamustine in com-bination with rituximab). It also had a greater gain in quality-adjusted life years (0.551 quality-adjusted life years gained compared to chlorambucil in combination with obinutuzumab and ibrutinib, 1.639 quality-adjusted life years gained compared to fludarabine in combination with cyclo-phosphamide and rituximab, and 1.186 quality-adjusted life years gained compared to bendamustine in combination with rituximab). Between 68% and 85% of the simulations performed in the sensitivity analysis showed that venetoclax in combination with obinutuzumab had lower costs and more quality-adjusted life years gained. Conclusions: Venetoclax in combination with obinutuzumab is an effi-cient and dominant alternative for treating previously untreated patients with chronic lymphocytic leukaemia compared to the available alterna-tives and from the perspective of the Spanish National Health System.