Matthew J. Maurer, Lasse H. Jakobsen, Raphael Mwangi, Norbert Schmitz, Umar Farooq, Cristopher R. Flowers, Peter de Nully Brown, Carrie A. Thompson, Henrik Frederiksen, David Cunningham, Judit Jørgensen, Viola Poeschel, Grzegorz Nowakowski, John F. Seymour, Francesco Merli, Corinne Haioun, Hervé Ghesquieres, Marita Ziepert, Hervé Tilly, Gilles Salles, Qian Shi, Tarec C. El‐Galaly, Thomas M. Habermann

Disease progression after frontline therapy for DLBCL is a clinically significant event. Patients who experience early progression or have refractory disease have especially poor outcomes. Simple, clinically applicable prognostic tools are needed for selecting patients for consideration for novel therapies and prognostication in the R/R setting. Model building was performed in patients from the SEAL consortium with disease progression after frontline immunochemotherapy. The primary endpoint was overall survival (OS) measured from date of progression. Validation was performed in the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource (MER) and Danish LYFO cohorts. Model performance was assessed using time-dependent concordance indices (c-statistic) and calibration with metrics evaluated at two years from progression. 1,234 of 5,112 patients treated with frontline immunochemotherapy in the SEAL consortium developed progressive disease. Time to progression on immunochemotherapy and age at progression were strongly associated with post-progression OS (both p<0.0001). A prognostic model was developed incorporating spline fit for both variables. The model had good concordance in the discovery (0.67) and validation sets (LYFO c=0.64, MER c=0.68) with generally good calibration. Time to progression on frontline therapy is strongly associated with post-progression OS in DLBCL. We developed and validated a simple to apply clinical prognostic tool in the R/R setting. The useful prediction of expected outcomes in R/R DLBCL and can inform treatment decisions such as considerations for CART therapy as well as trial designs. The model is available in smartphone-based point of care applications. This article is protected by copyright. All rights reserved.