OBJECTIVES: Patients with chronic lymphocytic leukemia (CLL) harboring TP53 aberrations (including del[17p] and mutations) and/or unmutated IGHV (IGHV-U) have inferior survival to standard first-line chemoimmunotherapies and should be considered for novel agents, such as ibrutinib. This study aims to evaluate the cost-effectiveness of predictive biomarker testing for first-line treatment in patients with CLL from an Australian healthcare system perspective.

METHODS: A cost-utility analysis using a decision tree and partitioned survival model assessed three testing strategies: (1) test for del(17p); (2) test for TP53; and (3) test for TP53 and IGHV. Based on the outcome of each strategy, the hypothetical cohort of patients were allocated to either first-line chemoimmunotherapy (low-risk) or ibrutinib (high-risk), with effectiveness modelled conditional on the molecular profile. Progression-free and overall survival were derived from literature using indirect treatment comparisons and survival analyses. Costs, utility, and adverse events were also estimated from published sources. Costs and quality-adjusted life-years (QALYs) were calculated over a lifetime horizon and discounted at 5% per annum. Deterministic and probabilistic sensitivity analyses quantified uncertainty and robustness of the results.

RESULTS: Simultaneous testing for TP53 and IGHV (Strategy 3) was the most effective (7.35 QALY) yet most costly (596,303 AUD) compared to testing for TP53 (Strategy 2: 6.06 QALY; 510,719 AUD) and del(17p) (Strategy 1: 5.95 QALY; 496,030 AUD). The incremental cost-effectiveness ratio of Strategy 3 compared to Strategy 1 was 71,939 AUD per QALY gained, with an estimated 35% and 65% probability of being cost-effective at a willingness-to-pay of 50,000 and 100,000 AUD per QALY gained, respectively.

CONCLUSIONS: Treatment risk-stratification using simultaneous assessment of TP53 and IGHV was associated with improved health outcomes and was cost-effective at a willingness-to-pay of 100,000 AUD per QALY gained.