A COST-EFFECTIVENESS ANALYSIS OF MINIMAL RESIDUAL DISEASE TESTING FOR THE MANAGEMENT OF CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA
Method: We developed a probabilistic state-transition microsimulation model to compare two strategies: MRD testing followed by risk-directed treatment versus no testing. The base case was a 6-year old child with newly diagnosed precursor B-cell ALL at the beginning of induction chemotherapy. We tracked changes in the risk of relapse after the first and second MRD tests at the end of induction and consolidation, respectively, to simulate patients’ prognosis and predict treatment in consolidation and maintenance phases. The analytic perspective was that of the Ontario Ministry of Health and Long-Term Care and the time horizon was the patient’s lifetime. The effect of MRD-risk-directed treatment intensification was based on the estimate of the UKALL2003 trial; other input parameters were estimated from the literature, expert opinion and a paediatric population-based clinical networked information system (POGONIS). Outcomes were expressed as the lifetime probability of relapse or bone marrow transplant (BMT), survival, quality-adjusted life years (QALYs), lifetime costs and incremental cost-effectiveness ratios. Costs and QALYs were discounted at 5%.
Result: MRD testing versus no testing was associated with increased life expectancy (66.50 vs. 66.04 years) and lower rates of first relapse or first BMT (relapse: 40.08% vs. 41.37%; BMT: 20.97% vs. 21.07%). Compared to no testing, MRD testing was associated with an increased quality-adjusted survival of 0.08 QALYs (95% confidence interval [CI]: -0.29; 0.46) and incremental costs of $3,863 (95%CI: -8,498; 15,530), yielding an incremental cost-effectiveness ratio of $50,249/QALY gained. The results were sensitive to the effectiveness of MRD-risk directed treatment, costs of ALL treatment and probability of BMT after consolidation. The probability that MRD testing was cost-effective was 57.80% at a threshold of $100,000/QALY.
Conclusion: MRD testing of newly diagnosed patients with childhood ALL followed by risk- directed treatment results in better health outcomes and appears to be cost-effective with a considerable degree of uncertainty.