Abstract

To estimate the cost-effectiveness of venetoclax + rituximab (VEN + R) in the treatment of relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) from a US-payer perspective. A three-state partitioned-survival model was used to extrapolate progression-free survival and overall survival (OS) over a lifetime horizon. Cost-effectiveness was estimated comparing 24-month fixed duration of VEN +R versus (vs.) bendamustine + rituximab (BR) based on the MURANO clinical trial (NCT02005471). Other comparators included ibrutinib (IBR), IBR + BR, and idelalisib + rituximab (IR). Relative efficacy of VEN+R vs. other comparators was estimated using matched-adjusted indirect comparisons. Health state utilities and adverse event disutilities were derived from published sources. Costs included CLL treatment, routine care and monitoring, adverse events, disease progression costs, and end of life care. Uncertainty was tested through deterministic, probabilistic, and scenario analyses. The incremental benefits measured in quality-adjusted life years (QALYs) for VEN+R were: 4.43 vs. IR, 2.83 vs. BR, 2.31 vs. IBR, and 1.43 vs. IBR+BR. Oral treat-to-progression agents incurred incremental costs: $705,318 for IBR+BR, $406,818 for IBR, and $17,065 for IR. Compared to these treatments VEN+R is more efficacious and has lower total costs ($486,606), or “dominates” them. Compared to BR, VEN+R is more costly (incremental cost: $175,591) resulting in an estimated incremental cost-effectiveness ratio of approximately $62,000 per QALY gained. At a willingness-to-pay of $150K/QALY, VEN+R was 88% likely to be cost-effective. Sensitivity analysis indicated the OS hazard ratio was the most influential parameter on the model outcomes. VEN+R is projected to be cost-effective vs. BR within accepted US cost-effectiveness thresholds. Compared with other treat-to-progression oral agents (IBR, IBR + BR, and IR) a 24-month fixed duration treatment option with VEN+R is more efficacious and cost saving. For R/R CLL patients, VEN+R is a cost-effective treatment and should be considered as a standard treatment option.

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