Cost‐Effectiveness of Venetoclax‐Based Treatment in Treatment‐Naïve Fit Patients With CLL Without TP53 Aberrations

The GAIA‐CLL13 trial showed that venetoclax‐obinutuzumab (Ven‐O) based regimens, with or without ibrutinib, offer superior efficacy compared to chemoimmunotherapy (CIT) with regards to progression free survival (PFS) in fit, treatment‐naïve (TN) CLL patients. However, their higher costs warrant a cost‐effectiveness evaluation. This study assessed the cost‐effectiveness of Ven‐O versus venetoclax with rituximab (Ven‐R), venetoclax‐obinutuzumab‐ibrutinib (Ven‐O‐I), and CIT in fit, TN CLL patients without TP53 aberrations across the Netherlands, Norway, and Denmark. A state‐transition Markov model including later line treatment was applied to estimate costs, life years (LYs), and quality‐adjusted life years (QALYs) over a 38‐year horizon. Results were sensitive to long‐term OS assumptions. In the base‐case analysis, extrapolating OS and PFS for each treatment separately, all venetoclax‐based treatments appeared cost‐effective compared to CIT in all three countries. ICERs for Ven‐R, Ven‐O, and Ven‐O‐I versus CIT were €35 840, €32 513, €30 331 for the Netherlands, €39 881, €38 099, €26 381 for Norway, and €34 010, €37 804, €33 215 for Denmark. In the sensitivity analyses, however, cost‐effectiveness was lost when only allowing separate OS and PFS extrapolations for statistically significant differences at 60‐month follow‐up. Furthermore, cost‐effectiveness results were sensitive to varying assumptions about national willingness‐to‐pay (WTP) thresholds, IGHV‐status, and time horizon. In conclusion, venetoclax‐based treatments may be considered a cost‐effective treatment option for fit, TN CLL patients without TP53 aberrations in the Netherlands, Norway, and Denmark, but the pricing process for targeted agents should take the uncertainty about cost‐effectiveness into account when negotiating pricing of medication. Longer follow‐up data is needed to address the uncertainties.