Cost-Effectiveness of Chimeric Antigen Receptor T-Cell Therapy in Pediatric Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia

Abstract

Background: Chimeric antigen receptor T-cell (CAR-T) therapy is a promising new class of cancer therapy but has a high up-front cost. We evaluated the cost-effectiveness of CAR-T therapy among pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL).

Methods: We built a microsimulation model for pediatric patients with relapsed/refractory B-ALL receiving either CAR-T therapy or standard of care. Outcomes included costs, quality of life (health utility), complications, and survival. We measured cost-effectiveness with the incremental cost-effectiveness ratio (ICER), with ICERs under $100 000 per quality-adjusted life-year (QALY) considered cost effective. One-way and probabilistic sensitivity analyses were used to test model uncertainty.

Results: Compared to standard of care, CAR-T therapy increased overall cost by $528 200 and improved effectiveness by 8.18 QALYs, resulting in an ICER of $64 600/QALY. The model was sensitive to assumptions about long-term CAR-T survival, the complete remission rate of CAR-T patients, and the health utility of long-term survivors. The base model assumed a 76.0% one-year survival with CAR-T, although if this decreased to 57.8%, then CAR-T was no longer cost effective. If the complete remission rate of CAR-T recipients decreased from 81% to 56.2%, or if the health utility of disease-free survivors decreased from 0.94 to 0.66, then CAR-T was no longer cost effective. Probabilistic sensitivity analysis found that CAR-T was cost effective in 94.8% of iterations at a willingness to pay of $100 000/QALY.

Conclusion: CAR-T therapy may represent a cost-effective option for pediatric relapsed/refractory B-ALL, although longer follow-up of CAR-T survivors is required to confirm validity of these findings.

Figure 1.

State-transition diagram. This figure demonstrates the primary disease states (ovals) of the microsimulation cost-effectiveness model. Arrows represent possible transitions from one health state to the next. Patients may experience toxicity and remain in their same state after acquiring a health utility deduction and cost penalty. Patients who initially received CAR-T but experienced disease progression received the standard therapy as salvage. ALL = acute lymphoblastic leukemia; CAR-T = chimeric antigen receptor T cell.

Figure 2.

Model validation. This figure demonstrates the internal validation of the cost-effectiveness model. The top panel (plot) demonstrates how our model (dotted lines) predicts survival compared with the published clinical data from the Maude (11) and Hijiya (17) trials (superimposed). The bottom panel (table) demonstrates how our model predicts overall survival, disease progression, and major toxicities compared with the Maude and Hijiya trials. CAR-T = chimeric antigen receptor T cell; CRS = cytokine release syndrome; SOC = standard of care.

Figure 3.

One-way sensitivity analysis. These plots depict the cost-effectiveness of chimeric antigen receptor T-cell (CAR-T) therapy compared to standard therapy as measured with the incremental cost-effectiveness ratio. The dashed line reflects the willingness-to-pay threshold of $100 000, with values below this line considered cost effective. Individual plots show how the cost-effectiveness of CAR-T therapy varies by (A) CAR-T 1-year overall survival, (B) CAR-T complete remission rate, and (C) Health utility of disease-free health state. QALY = quality-adjusted life-year.

Figure 4.

Probabilistic sensitivity analysis. This plot demonstrates a cost-effectiveness acceptability curve. The plot shows the results of a probabilistic sensitivity analysis comparing the cost-effectiveness of chimeric antigen receptor T-cell (CAR-T) therapy with standard therapy for pediatric relapsed/refractory B-cell acute lymphoblastic leukemia. The gray dotted line reflects the willingness to pay threshold of $100 000 per quality-adjusted life-year (QALY).