An Oncology Simulation Model to Estimate 10-Year Progression-Free Survival and Overall Survival Based on the 5-Year Update from the ECHELON-2 Trial in Frontline Patients with Peripheral T-Cell Lymphoma: A United States Perspective
Authors: Burke John M. , Yu Kristina S. , Mordi Uche , Bloudek Brian , Liu Nicholas , Fanale Michelle A. , Phillips Tycel 
Published: November 2021

Abstract
Objectives
Peripheral T-cell lymphomas (PTCLs) are a rare and aggressive type of non-Hodgkin lymphoma (NHL) associated with a poor prognosis. Common frontline (1L) regimens include brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A+CHP), and cyclophosphamide, doxorubicin, vincristine, and prednisone with or without the addition of etoposide (CHOP and CHOEP, respectively). Based on the 5-year update of the ECHELON-2 trial, patients with previously untreated CD30-expressing PTCL on A+CHP continued to demonstrate clinically meaningful improvements in progression-free survival (PFS) and overall survival (OS) compared with CHOP. Our objective was to estimate the future number of patients alive and progression free with A+CHP over 10-years, based on the 5-year follow-up results from ECHELON-2.
Methods
An oncology simulation model, from the United States perspective, was developed with a 1-month cycle length that estimates population-level outcomes of PTCL patients based on disease incidence, treatment patterns, PFS, and OS of commonly used regimens for PTCL. Incidence of PTCL, 19.26 cases per 100,000 persons, was derived using Surveillance, Epidemiology and End Results (SEER) estimates for NHL in 2020 and the estimated proportion of PTCL cases (~4%) within the NHL category, provided by the Lymphoma Research Foundation. To populate the base case model, treatment patterns following 1L utilization of CHOP (65%) and CHOEP (35%) were varied over time and compared to A+CHP (40%). The model also includes a portion of patients in remission in 1L who are eligible to receive transplant therapy. Additional model inputs were derived from: 1) ECHELON-2, with 5-year PFS rates of 51.4% (95% CI 42.8, 59.4) for A+CHP, 43.0% (95% CI 35.8, 50.0) for CHOP, and OS HR 0.72 (95% 0.53, 0.99); 2) published literature to inform PFS for consolidation and subsequent lines of therapy; and 3) expert clinicians' opinion on commonly used regimens for relapsed/refractory PTCL (included in the model were brentuximab vedotin, romidepsin, pralatrexate, ifosfamide in combination with carboplatin and etoposide [ICE], and gemcitabine-based regimens). Annual prevalence of patients living progression-free with PTCL in the 1L setting with each prescribed scenario was estimated for 10 years (year 2031) with and without the availability of A+CHP.
Results
The cumulative number of patients with newly diagnosed PTCL between 2026 and 2031 was estimated at 8,020. The number of patients alive and progression-free based on 1L treatment was estimated at 6,304 in a scenario without A+CHP and 7,414 with A+CHP (Δ+1,110, 17.6% increase) in 2031. It was also estimated that 1,203 patients would progress to second-line treatment with CHOP vs 1,119 patients with 1L A+CHP (Δ-84, 7.0% decrease) in 2031.
Conclusions
The durable and significant improvements in PFS and OS of A+CHP vs CHOP in the 5-year follow-up data from ECHELON-2 estimated an increase in the number of 1L PTCL patients who remain progression free and alive for greater than 10 years. This improvement in outcomes may translate into an increased prevalence of PTCL patients, reflecting an increased number of patients in remission and options to undergo transplant therapy when necessary.

Disclosures
Burke: Adaptive Biotechnologies: Consultancy; AstraZeneca: Consultancy; Roche/Genentech: Consultancy; SeaGen: Consultancy, Speakers Bureau; Beigene: Consultancy, Speakers Bureau; Epizyme: Consultancy; AbbVie: Consultancy; Bristol Myers Squibb: Consultancy; X4 Pharmaceuticals: Consultancy; Kymera: Consultancy; MorphoSys: Consultancy; Kura: Consultancy; Verastem: 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. Phillips: Genentech: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Bayer: Consultancy, Research Funding; AstraZeneca: Consultancy; Incyte: Consultancy, Other: received travel expenses from Incyte, Research Funding; ADCT, BeiGene, Bristol Myers Squibb, Cardinal Health, Incyte, Karyopharm, Morphosys, Pharmacyclics, Seattle Genetics: Consultancy.