Cost-Effectiveness Analysis of Venetoclax in Combination with Azacitidine Versus Azacitidine Monotherapy in Patients with Acute Myeloid Leukemia Who are Ineligible for Intensive Chemotherapy: From a US Third Party Payer Perspective

Abstract

Objectives: Using individual patient-level data from the phase 3 VIALE-A trial, this study assessed the cost-effectiveness of venetoclax in combination with azacitidine compared with azacitidine monotherapy for patients newly diagnosed with acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy, from a United States (US) third-party payer perspective.

Methods: A partitioned survival model with a 28-day cycle and three health states (event-free survival (EFS), progressive/relapsed disease, and death) was developed to estimate costs and effectiveness of venetoclax + azacitidine versus azacitidine over a lifetime (25-year) horizon. Efficacy inputs (overall survival (OS), EFS, and complete remission (CR)/CR with incomplete marrow recovery (CRi) rate) were estimated using VIALE-A data. Best-fit parametric models per Akaike Information Criterion were used to extrapolate OS until reaching EFS and extrapolate EFS until Year 5. Within EFS, the time spent in CR/CRi was estimated by applying the CR/CRi rate to the EFS curve. Past Year 5, patients still in EFS were considered cured and to have the same mortality as the US general population. Mean time on treatment (ToT) for both regimens was based on the time observed in VIALE-A. Costs of drug acquisition, drug administration (initial and subsequent treatments), subsequent stem cell transplant procedures, adverse events (AEs), and healthcare resource utilization (HRU) associated with health states were obtained from the literature/public data and inflated to 2021 US dollars. Health state utilities were estimated using EuroQol-5 dimension-5 level data from VIALE-A; AE disutilities were obtained from the literature. Incremental cost-effectiveness ratios (ICERs) per life-year (LY) and quality-adjusted life-year (QALY) gained were estimated. Deterministic sensitivity analyses (DSA), scenario analyses, and probabilistic sensitivity analyses (PSA) were also performed.

Results: Over a lifetime horizon, venetoclax + azacitidine versus azacitidine led to gains of 1.89 LYs (2.99 vs. 1.10, respectively) and 1.45 QALYs (2.30 vs. 0.84, respectively). Patients receiving venetoclax + azacitidine incurred higher total lifetime costs ($250,486 vs. $110,034 (azacitidine)). The ICERs for venetoclax + azacitidine versus azacitidine were estimated at $74,141 per LY and $96,579 per QALY gained. Results from the DSA and scenario analyses supported the base-case findings, with ICERs ranging from $60,718 to $138,554 per QALY gained. The results were most sensitive to varying the parameters for the venetoclax + azacitidine base-case EFS parametric function (Gompertz), followed by alternative approaches for ToT estimation, treatment costs of venetoclax + azacitidine, standard mortality rate value and ToT estimation, alternative sources to inform HRU, different cure modeling assumptions, and the parameters for the venetoclax + azacitidine base-case OS parametric function (log-normal). Results from the PSA showed that, compared with azacitidine, venetoclax + azacitidine was cost-effective in 99.9% of cases at a willingness-to-pay threshold of $150,000 per QALY.

Conclusions: This analysis suggests that venetoclax + azacitidine offers a cost-effective strategy in the treatment of patients with newly diagnosed AML who are ineligible for intensive chemotherapy from a US third-party payer perspective.

Trial registration: ClinicalTrials.gov, NCT02993523. Date of registration: 15 December 2016.

Conflict of interest statement

Keith W. Pratz is an associate professor of medicine at the Hospital of the University of Pennsylvania. Keith W. Pratz has received honoraria or consultancy fees from AbbVie, Astellas, Boston BioMedical, Jazz Pharmaceuticals, STI Pharmaceuticals, and Celgene; and institutional research funding from AbbVie, Astellas, Agios, and Millennium. Xinglei Chai, Jipan Xie, Lei Yin, and Xiaoyu Nie are employees of Analysis Group, Inc., which has received consulting fees from Genentech, Inc. Melissa Montez, Erica Iantuono, Lisa Downs, and Esprit Ma are employees of Genentech, Inc. and hold stock/options.

© 2022. The Author(s).

Figures

Fig. 1

Model structure. CR complete remission, CRi complete remission with incomplete marrow recovery, EFS event-free survival, PD/RL progressive disease/relapse

Fig. 2

Deterministic sensitivity analysis (DSA) and scenario analysis sensitivity results: Top 30 drivers of incremental cost per quality-adjusted life-year (QALY) gained for venetoclax + azacitidine versus azacitidine. Costs listed in 2021 US dollars. AE adverse event, AIC Akaike Information Criterion, CI confidence interval, CR complete remission, CRi complete remission with incomplete marrow recovery, EFS event-free survival, HR hazard ratio, HRU healthcare resource utilization, NICE National Institute for Health and Care Excellence, OS overall survival, PD/RL progressive disease/relapse, SMR standard mortality rate, ToT time on treatment, US United States

Fig. 3

Probabilistic sensitivity analysis (PSA) results: Incremental cost-effectiveness plane (a) and cost-effectiveness acceptance curve (b) for venetoclax + azacitidine versus azacitidine. The red line indicates the willingness-to-pay threshold of $150,000 per QALY gained. ICER incremental cost-effectiveness ratio, QALY quality-adjusted life-year