Progression-Free Survival as a Surrogate End Point for Overall Survival in First-Line Diffuse Large B-Cell Lymphoma: An Individual Patient-Level Analysis of Multiple Randomized Trials (SEAL)

PurposeOverall survival (OS) is the definitive and best-established primary efficacy end point to evaluate diffuse large B-cell lymphoma (DLBCL) therapies, but it requires prolonged follow-up. An earlier end point assessed post-treatment would expedite clinical trial conduct and accelerate patient access to effective new therapies. Our objective was to formally evaluate progression-free survival (PFS) and PFS at 24 months (PFS24) as surrogate end points for OS in first-line DLBCL.Patients and MethodsIndividual patient data were analyzed from 7,507 patients from 13 multicenter randomized controlled trials of active treatment in previously untreated DLBCL, published after 2002, with sufficient PFS data to predict treatment effects on OS. Trial-level surrogacy examining the correlation of treatment effect estimates of PFS/PFS24 and OS was evaluated using both linear regression (R2WLS) and Copula bivariable (R2Copula) models. Prespecified criteria for surrogacy required either R2WLS or R2Copula ≥ 0.80 and nei...