Cost-Effectiveness of Polatuzumab Vedotin Plus Bendamustine-Rituximab for Transplant-Ineligible Relapsed/Refractory Diffuse Large B-Cell Lymphoma in the United States
Authors: Betts Keith A , Felizzi Federico , Dieye Ibou , Li Jia , Schulz Mathias , Hong Samuel J , Masaquel Anthony S 
Published: February 2021

Introduction
Polatuzumab vedotin (pola), a first-in-class CD79b-targeted antibody-drug conjugate, was recently approved by the United States (US) Food and Drug Administration (June 2019) in combination with bendamustine-rituximab (BR) for the treatment of adults with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) after at least two prior therapies. Approval was based on the results of a randomized Phase II trial (GO29365/NCT02257567) in which pola+BR demonstrated clinically meaningful improvements in complete response (CR) rates (40.0% vs 17.5%, respectively), progression-free survival (PFS; hazard ratio [HR], 0.36; 95% confidence interval [CI]: 0.21-0.63) and overall survival (OS; HR, 0.42; 95% CI: 0.24-0.75) versus BR alone in transplant-ineligible R/R DLBCL (Sehn et al. J Clin Oncol 2020).
Objective
To evaluate the cost-effectiveness of pola+BR in R/R DLBCL from a US payer's perspective, using 140mg and 30mg single-dose vials of pola and GO29365/NCT02257567 study data.
Methods
A partitioned survival model was developed to estimate the economic and health-related quality of life impact of pola+BR versus BR alone in transplant-ineligible R/R DLBCL. A lifetime horizon and 3% discount rate were considered for costs and outcomes. Clinical data (PFS, OS, drug utilization, treatment duration and adverse events [AEs]) were sourced from the GO29365/NCT02257567 study. Costs included drug acquisition/administration, AE management, PFS routine care, progressive disease (PD) medical care and end-of-life care. Quality-adjusted life-years (QALYs) were calculated using published utility estimates (Tisagenlecleucel, NICE Report 2019). The base-case analysis assumed OS was informed by PFS (extrapolated) and used a mixture cure rate model to estimate the proportion of putative long-term survivors (pola+BR: 21%; BR: 0% [Sehn et al. ICML 2019]). Deterministic and probabilistic sensitivity analyses (PSA) and scenario analyses (mixture cure rate model with OS modelled separately from PFS, and standard parametric survival models) were performed to assess uncertainty.
Results
The total cost of pola+BR ($210,418) was $92,329 higher than BR ($118,089), primarily due to higher drug/administration costs ($139,717 vs $47,944, respectively). Pola+BR reflected cost-savings for PD medical care (-$4,849) and end-of-life care (-$2,248) versus BR. Costs due to AE management were $6,484 higher for pola+BR ($21,989) than BR ($15,505). Treatment with pola+BR was associated with an additional 2.57 QALYs versus BR. The incremental cost-effectiveness ratio (ICER) was $35,864/QALY gained. The ICER was most sensitive to survival modelling assumptions, the discount rate considered for effectiveness, and utility in PFS. Results of the PSA showed that pola+BR was cost-effective versus BR in 68% and 97% of cases using a willingness-to-pay threshold of $50,000 and $100,000, respectively. Scenario analyses resulted in ICERs ranging from $41,442/QALY (mixture cure with OS modelled separately from PFS) to $72,166/QALY (standard parametric).
Conclusions
This updated cost-effectiveness analysis includes 30mg single-dose vials of pola in addition to the original 140mg vials, allowing more precise weight-based dosing. Driven predominantly by higher PFS/OS and the higher estimated proportion of long-term survivors, results suggest that in the US, pola+BR versus BR is cost-effective for the treatment of adults with transplant-ineligible R/R DLBCL.

Disclosures
Betts: Genentech, Inc.: Research Funding. Felizzi:F. Hoffmann-La Roche Ltd: Current Employment. Dieye:Analysis Group: Current Employment. Li:F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company; Genentech Inc.: Current Employment. Schulz:F. Hoffmann-La Roche Ltd: Current equity holder in private company; Genentech, Inc.: Current Employment. Hong:Genentech, Inc.: Current Employment; Karuna Therapeutics: Current equity holder in publicly-traded company; Y-mAbs Therapeutics: Current equity holder in publicly-traded company; Astellas Pharma: Ended employment in the past 24 months. Masaquel:Analysis Group: Current Employment.