Cost‐Effectiveness of Venetoclax‐Based Treatment in Treatment‐Naïve Fit Patients With <scp>CLL</scp> Without <scp>TP53</scp> 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.