Abstract
•LEO-MER real-world prospective cohort study shows that systemic PTCLs remain highly heterogeneous, with poor outcomes in most subtypes.•Minimal change in survival rates over the last two decades emphasizes the unmet clinical need for novel therapeutic approaches in PTCL.
Few prospective benchmark studies exist to characterize the evolving contemporary real-world practice for PTCL. We report the patterns of first-line care and outcomes for 720 patients with systemic PTCL enrolled in two related prospective cohort studies, LEO from 2015-2020 (ClinicalTrials.gov NCT02736357) and MER from 2002-2015, both followed through 2024. The primary endpoints were EFS and OS using Kaplan-Meier estimator and Cox regression model. Secondary endpoints included correlations of clinical and treatment factors with survival. The most common induction regimens were CHOP-based (70%), given as CHOP (36%), CHOP plus etoposide (23%), or CHOP-like plus novel agents (11.5%, including 5% BV-CHP). Consolidative autologous stem cell transplant was performed in 102 patients (14%). Within nodal PTCL, EFS and OS were adversely associated with IPI 2-5 (HR=2.00, 95%CI: 1.59–2.52 for EFS; HR=2.44, 95%CI: 1.86–3.19 for OS), PIT 1-4 (HR=3.02, 95%CI 2.07-4.39 for EFS; HR=5.10, 95%CI 3.01-8.63 for OS), and non-ALCL subtypes (HR=2.97, 95%CI: 2.26–3.91 for EFS; HR=3.71, 95%CI: 2.65–5.20 for OS). Within LEO, which captured increasing first-line etoposide and BV, adding etoposide to CHOP was associated with better OS in ALK-negative ALCL (HR=0.14, 95%CI: 0.03-0.69, p=0.015). BV-CHP showed a trend toward OS improvement in ALCL (HR=0.15, 95%CI 0.02-1.19, p=0.073). Patients failing EFS6 and EFS24 had 5-year subsequent OS of 12% (95% CI: 7.8%, 19%) and 17% (95% CI: 13%, 22%), respectively. The inferior outcomes in non-ALCL subtypes and patients failing EFS6 and EFS24 highlight unmet needs with CHOP-based induction, where clinical trials with targeted therapy should be prioritized.