An Oncology Simulation Model to Estimate 10-Year Progression-Free Survival and Stem Cell Transplantation for Frontline, Stage III or IV Classical Hodgkin Lymphoma Based on the 5-Year Update of the ECHELON-1 Trial: A United States Perspective
Authors: Phillips Tycel , Migliaccio-Walle Kristen , Yu Kristina S. , Bloudek Brian , Liu Nicholas , Fanale Michelle A. , Burke John M. 
Published: November 2021

Abstract
Objectives
Doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) is the most common frontline (1L) regimen for patients with stage III or IV classical Hodgkin lymphoma (cHL), but about 30% of patients with stage III or IV cHL have refractory or relapsed disease after ABVD treatment. Based on the 5-year update of the ECHELON-1 trial, patients on 1L brentuximab vedotin, doxorubicin, vinblastine and dacarbazine (A+AVD) continued to demonstrate a robust and durable progression-free survival (PFS) improvement vs ABVD with a 32% reduction in the risk of progression or death (HR=0.681, nominal P=0.002). Our objective was to estimate the future number of patients with cHL who are alive and progression-free over 10-years with 1L A+AVD, based on the 5-year follow-up results from ECHELON-1.
Methods
An oncology simulation model, from the United States perspective, was developed with a 1-month cycle length that estimates population-level outcomes based on annual prevalence of cHL, considering disease incidence, treatment patterns, PFS, and overall survival of commonly used treatment regimens for stage III or IV cHL. Incidence of cHL was derived from the 2019 Surveillance, Epidemiology, and End Results (SEER) 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 to A+AVD (24%). For every model cycle, patients who experienced disease progression on 1L therapy discontinued therapy and transitioned to second-line (salvage) therapy. The transition from second-line therapy to transplant is also included in the model based on patient eligibility. Model inputs were informed by 1) real-world treatment utilization; 2) treatment-specific clinical trial data, including ECHELON-1 with 5-year PFS rates of 75.3% for ABVD (95% CI: 70.0, 85.0) and 82.2% for A+AVD (95% CI: 71.7, 78.5); and 3) expert clinicians' opinions. Annual prevalence of patients living progression-free with cHL in the 1L setting with each prescribing scenario was estimated for 10 years (year 2031) with and without the availability of A+AVD.
Results
The annual number of newly diagnosed patients with stage III or IV cHL at 10 years in 2031 was estimated at 3,586. The number of patients alive and progression-free in the 1L setting was 19,494 without A+AVD and 19,660 with A+AVD (Δ+166, 0.85% increase) in 2031. Overall, for every 100 patients prescribed A+AVD, it was predicted that an additional 6.5 patients per year achieved at least 5 years PFS and 4.2 to 4.7 fewer patients per year required a stem cell transplant (SCT), based on the 70% to 80% of eligible patient proceeding to SCT, respectively.
Conclusions
The durable PFS improvement of A+AVD vs ABVD in the 5-year follow-up data from ECHELON-1 resulted in increasing the number of patients with stage III or IV cHL who remain progression free for greater than 10 years and reducing future SCTs, based on this oncology simulation model for cHL. The significant improvement in PFS observed in the 5-year ECHELON-1 trial may translate to fewer patients with cHL developing primary refractory or relapsed disease and reduce the need for additional therapies including SCT.

Disclosures
Phillips: Genentech: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Research Funding; Bayer: Consultancy, Research Funding; Incyte: Consultancy, Other: received travel expenses from Incyte, Research Funding; ADCT, BeiGene, Bristol Myers Squibb, Cardinal Health, Incyte, Karyopharm, Morphosys, Pharmacyclics, Seattle Genetics: Consultancy; AbbVie: Consultancy, Research Funding; AstraZeneca: Consultancy. Migliaccio-Walle: Seagen, Inc: Consultancy. Yu: Seagen, Inc: Current Employment, Current equity holder in publicly-traded company. Bloudek: Seagen, Inc: Consultancy. Liu: Seagen, Inc: Current Employment, Current equity holder in publicly-traded company. Fanale: Seagen, Inc: Current Employment, Current equity holder in publicly-traded company. Burke: Beigene: Consultancy, Speakers Bureau; Verastem: Consultancy; Kymera: Consultancy; Bristol Myers Squibb: Consultancy; Adaptive Biotechnologies: Consultancy; MorphoSys: Consultancy; AstraZeneca: Consultancy; Roche/Genentech: Consultancy; Kura: Consultancy; Epizyme: Consultancy; X4 Pharmaceuticals: Consultancy; SeaGen: Consultancy, Speakers Bureau; AbbVie: Consultancy.