Cost-Effectiveness of CPX-351 Versus 7+3 Regimen in the Treatment of Treatment-Related Acute Myeloid Leukemia (tAML) or AML with Myelodysplasia-Related Changes (MRC)

CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin that delivers a synergistic drug ratio. In a phase 3 trial (NCT01696084) in elderly patients with newly diagnosed tAML or AML-MRC, CPX-351 demonstrated superior overall survival (9.56 vs 5.95 months; HR = 0.69; P= 0.005) and significantly improved complete remission rate (38% vs 26%; P= 0.040) compared to the 7+3 regimen of cytarabine and daunorubicin, the current standard of care for remission induction. These clinical improvements may increase the cost of caring for patients with AML through higher drug costs, increased numbers of patients receiving hematopoietic cell transplant (HCT), and the costs of disease management during extended survival. In an era of increased scrutiny of drug costs and health care budgets, it is essential to understand the balance of clinical benefits and costs associated with treatment of AML using CPX-351.

A health economic model with a lifetime time horizon was developed comparing the costs and outcomes of CPX-351 to those of 7+3 in the treatment of AML from the perspective of a US commercial payer. The model was developed in accordance with good modeling practice guidelines and recommendations of the US Second Panel on Cost-Effectiveness in Health and Medicine. The model considered a patient population stratified by age and AML subtype based on the CPX-351 phase 3 clinical trial design. Within each subpopulation, patients were distributed among potential treatment pathways in accordance with observed trial data. Treatment pathways in the model were defined in terms of whether or not patients responded following induction and whether or not patients received an HCT. The numbers of induction and consolidation cycles were also tracked. The model then projected overall and event-free survival over patients' lifetimes based on the patients' characteristics and treatment pathways using statistical extrapolation of observed data from the clinical trial. Specifically, for each treatment pathway, a parametric survival function was fit to the observed data with patient characteristics, treatment arm, cycles of induction, and cycles of consolidation included as risk factors. These survival functions were then applied in the model for each subpopulation and summed to estimate the overall clinical outcomes for the full population. Costs of drugs were assigned based on published sources for 7+3 and manufacturers' estimates for CPX-351. Costs of non-pharmaceutical management were estimated based on DRG coding and published literature. Quality of life at different disease stages was assessed using the time trade-off method in vignette-based interviews.

We found that treatment with CPX-351 was projected to provide an additional 1.9 years of life compared to 7+3 (2.8 vs 0.9 years, respectively). These gains reflected shifts among the treatment pathways, particularly a larger fraction of patients receiving HCT with CPX-351 than with 7+3, and longer survival within pathways among patients who responded to induction therapy. While the CPX-351 treatment arm demonstrated increased numbers of responders, non-responders had no difference in outcomes between the arms in the model. When accounting for the quality of life of patients with different stages of AML, the additional life years were equivalent to an incremental increase of 1.02 quality-adjusted life years (QALYs) compared to 7+3. Patients in the CPX-351 arm incurred a total incremental cost of $113,658 compared to 7+3, primarily due to pharmacy costs and costs associated with the larger number of HCTs. Taken together, these costs and improved clinical outcomes yield an incremental cost-effectiveness ratio (ICER) of $111,385/QALY gained over 7+3.

These results suggest a favorable balance between the clinical gains and incremental costs of treatment with CPX-351 versus the 7+3 standard of care and demonstrate that CPX-351 is a cost-effective option in the treatment of patients with tAML or AML-MRC.