Cost-Effectiveness Analysis of Consolidation with Brentuximab Vendotin Versus Active Surveillance in Individuals with High-Risk Hodgkin Lymphoma Undergoing High Dose Chemotherapy with Stem Cell Rescue
Authors: Hui Lucy , von Keudell Gottfried , Wang Rong , Zeidan Amer M. , Gore Steven D. , Ma Xiaomei , Davidoff Amy J. , Huntington Scott F 
Published: October 2019

Abstract
Introduction
Although the majority of individuals diagnosed with Hodgkin's lymphoma (HL) are cured with first-line therapy, upwards of 20-30% of patients experience primary refractory disease or relapse after achieving remission. Autologous stem cell transplantation (ASCT) remains a curative option for R/R HL, but approximately 50% will experience HL recurrence followingASCT. A recent randomized double-blind trial (ATHERA) found post-ASCTconsolidation treatment with 16 cycles ofbrentuximabvedotin(BV) decreased the risk of HL progression compared to placebo. However, the impact of BV consolidation on overall survival, quality of life, and health care costs remains to be elucidated.
Methods
We constructed a Markov decision-analytic model from the US societal perspective to compare the costs and clinical outcomes associated with post-ASCTBV consolidation versus active surveillance with BV at time of HL progression. Patients entered our post-ASCTmodel receiving BV consolidation or active surveillance, with 4 additional 3-month health transition states used to model care until death (Figure 1). Results from theATHERAtrial informed the majority of our health state transition probabilities and our cohort characteristics.Rates of HL progression followingASCTwere extrapolated to 5 years using standard parametric modeling of reconstructed individual patient data derived from publishedATHERAresults.Our model also incorporated a number of recently published studies, including long term follow-up data of BV monotherapy in the salvage setting and separate reports supporting the use ofnivolumabfor R/R HL. All drug costs were calculated at 106% of average sales price and administrative costs were derived from the Medicare fee schedule. All future costs and benefits were discounted at 3% annually and a lifetime horizon was used to estimate cumulative healthcare costs and health utilities. Quality-adjusted utility, lifetime costs, and incremental cost-effectiveness ratios (ICERs) were calculated for each post-ASCTstrategy.
Results
Reconstructed individual patient data from publishedATHERAresults was best fit using aGompertzdistribution. This parametric model predicted 5-year progression free survival to be 54% for BV consolidation compared to 43% for active surveillance. This reduction in HL progression translated intolonger overall survival (OS) for individuals receiving BV consolidation (mean [median] OS: 30.2 [36.6] vs 28.0 [29.9] years). After quality-of-life adjustments and standard future discounting, BV consolidation was associated with an improvement of 0.98 quality-adjusted-life years (QALYs) compared to active surveillance. However, the strategy of BV consolidation led to significantly higher healthcare costs ($330,833 vs $187,747), with anICERof $146,006/QALYfor BV consolidation compared to active surveillance. Model conclusions were stable on sensitivity analyses, including probabilistic sensitivity analysis where less than 5% of iterations found BV consolidation cost-effective at a level of $100,000/QALY.
Conclusions
Although consolidation treatment with BV followingASCTappears to reduce the risk of HL recurrence and prolong survival, the strategy is associated with significant health care costs compared to active surveillance. Our analysis suggests the use of BV as consolidation therapy at current US pricing ($137/mg) is unlikely to be cost-effective at a willingness to pay of $100,000/QALY. However, if indication-specific pricing were implemented, our model estimates BV price reductions of 20% to 40% for the post-ASCTconsolidative setting would translate toICERsof $100,000/QALYand $50,000/QALY, respectively. Thus, for effective therapies such as BV, moderate reductions in current prices may produce cost-effective strategies. Ultimately, future indication-specific and value-based pricing has the potential to not only align drug prices to their value, but also continue to reward highly effective and innovative cancer therapy.
Figure 1 Figure 1.

Disclosures
Zeidan: Ariad: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Incyte: Consultancy, Honoraria. Gore:Celgene: Consultancy, Honoraria, Research Funding. Ma:Celgene Corporation: Consultancy. Davidoff:PhRMA: Research Funding. Huntington:Celgene: Consultancy, Honoraria; Oncosec Medical: Equity Ownership; Exelixis: Equity Ownership; Johnson & Johnson: Consultancy; Pharmacyclics: Honoraria; Geron: Equity Ownership.