10-Year Impact on Productivity Costs Associated with Mortality in Stage III or IV Classical Hodgkin Lymphoma Based on the Overall Survival Update of the ECHELON-1 Trial: Application of an Oncology Simulation Model in the United States

BACKGROUND: Classical Hodgkin lymphoma (cHL) has a bimodal age distribution uniquely affecting younger individuals of working age as well as older adults. Consequently, Hodgkin lymphoma (HL) was predicted to have the second highest productivity costs (as measured by present value lifetime earnings [PVLE]) lost per death at $544,118 across site-specific cancers, with overall lost productivity costs over one year of $828,691,758 due to mortality among adults aged ≥20 years in the United States in 2010. For decades, doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) has been the standard of care frontline (1L) regimen for patients with stage III or IV cHL. However, 30% of patients with stage III or IV cHL have refractory or relapsed disease after ABVD treatment. The ECHELON-1 trial was the first trial to show an overall survival (OS) improvement against classic ABVD in patients receiving brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD), with a 41% reduction in the risk of death (HR: 0.59; 95% CI: 0.396-0.879; P=0.009), after a median follow-up of approximately 6 years. Our objective was to estimate the lifetime productivity impact due to mortality in patients newly diagnosed with stage III or IV cHL over 10-years in scenarios without and with 1L A+AVD, based on the OS results from ECHELON-1. METHODS: Individual productivity was estimated using the human capital approach and is expressed in terms of PVLE. Among patients newly diagnosed with stage III or IV cHL, PVLE was measured using published age- and sex-specific estimates of full- and part-time employment, and annual earnings. Number of deaths and life years saved without and with A+AVD were calculated using an oncology simulation model (OSM) developed to estimate population-level outcomes based on annual prevalence of cHL, considering disease incidence, treatment patterns, and OS of commonly used treatment regimens for stage III or IV cHL. Incidence of stage III and IV cHL was derived from the 2019 Surveillance, Epidemiology, and End Results Program, assuming 95% of HL is classical of which 41% is stage III or IV. To populate the base case model, treatment patterns following 1L use of ABVD (64.5%) and positron emission tomography (PET)-adapted therapy (35.5%) were varied over time and compared with A+AVD (27%). OSM inputs were informed by 1) real-world treatment utilization; 2) treatment-specific OS, including ECHELON-1 with a 41% reduction in the risk of death with A+AVD versus ABVD at approximately 6-years (HR: 0.59; 95% CI: 0.396-0.879; P=0.009); and 3) expert clinicians’ opinions. Annual prevalence of patients diagnosed with stage III or IV cHL over a 10-year period (year 2031) was estimated and downstream lifetime productivity costs (2022 US$) were projected without and with the availability of A+AVD. Scenario analyses varied A+AVD utilization from 40% to 80% as recommended by expert clinicians’ opinion. RESULTS: The annual number of newly diagnosed patients with stage III or IV cHL at 10 years in 2031 was estimated at 3,654. Over 10 years, the estimated total number of deaths was 2,650 without and 2,290 with A+AVD (Δ-360, 14% fewer deaths). The model predicted that, annually for every 100 patients prescribed A+AVD, 3.7 more deaths would be avoided. Considering patients newly diagnosed with stage III or IV cHL, the total PVLE lost over 10 years was estimated at $1.664 billion without A+AVD versus $1.438 billion with A+AVD (Δ$226 million, 14% decrease) in the base case (27% A+AVD utilization). This corresponded to a PVLE lost per death of $628,000. In scenario analyses, varying 1L A+AVD utilization from 40%-80% yielded a PVLE lost ranging from $1.331 billion (Δ$333 million, 20% decrease) to $1.137 billion (Δ$527 million, 32% decrease) vs the scenario without A+AVD. CONCLUSIONS: Lost productivity costs due to mortality in patients with stage III or IV cHL are high. Our model quantifies how increasing utilization of A+AVD compared with ABVD in stage III or IV cHL patients would reduce lost productivity costs due to deaths avoided, based on the OS results from ECHELON-1.