Search

Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is a genetic condition associated with significant morbidity and mortality. In this study we aimed to identify patient subgroups exhibiting the greatest health-related quality of life (HRQL) benefit from inotersen treatment.We examined data from the inotersen phase 2/3 randomized, controlled trial for ATTRv-PN, NEURO-TTR (NCT01737398, 66 weeks). LASSO regression models predicted changes in Norfolk QoL-DN total score (TQoL, range -4 to 136; higher scores indicate poorer HRQL) from baseline in the inotersen and placebo arm, respectively. Individualized efficacy scores (ES) were calculated as differences between predicted change scores had patients received inotersen vs placebo. Patients were ranked by ES to define the greatest-benefit subpopulation (top 50%). Characteristics of the top 50% and bottom 50% of patients were compared.The overall mean ± standard deviation TQoL change was -0.20 ± 19.13 for inotersen (indicating no change) and 10.77 ± 21.13 for placebo (indicating deterioration). Within the highest-benefit patients, mean TQoL change was -11.03 ± 17.06 (improvement) for inotersen and 11.24 ± 22.97 (deterioration) for placebo (P .001). Compared with the overall population, patients in the greatest-benefit subpopulation were younger, more likely to have polyneuropathy disability (PND) scores 1 or 2, less likely to have received prior tafamidis or diflunisal treatment, and more likely to have Val30Met mutations and higher (worse) baseline TQoL.Patients who were younger and/or at earlier polyneuropathy stages experienced greater HRQL benefits from inotersen over 66 weeks. These findings underscore the need for early diagnosis and treatment initiation, especially among more severely affected patients in early stages of ATTRv-PN.

Aim: To evaluate the cost–effectiveness of polatuzumab vedotin (pola) + bendamustine + rituximab (BR) in relapsed/refractory diffuse large B-cell lymphoma based on the GO29365 trial from a US payer’s perspective. Materials & methods: A partitioned survival model used progression-free survival and overall survival data from the GO29365 trial. The base case analysis assumed overall survival was informed by progression-free survival; a mixture cure model estimated proportion of long-term survivors. Results: In the base case, pola + BR was cost-effective versus BR at US$35,864 per quality-adjusted life year gained. Probabilistic and one-way sensitivity analyses showed that the findings were robust. Conclusion: Pola + BR is cost-effective versus BR for the treatment of transplant-ineligible relapsed/refractory diffuse large B-cell lymphoma in the US.

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.