Relapsed/Refractory International Prognostic Index (R/R‐IPI): An international prognostic calculator for relapsed/refractory diffuse large B‐cell lymphoma

• Published in: American journal of hematology Vol. 96; no. 5; pp. 599 - 605
• Main Authors: Maurer, Matthew J., Jakobsen, Lasse H., Mwangi, Raphael, Schmitz, Norbert, Farooq, Umar, Flowers, Cristopher R., Nully Brown, Peter, Thompson, Carrie A., Frederiksen, Henrik, Cunningham, David, Jørgensen, Judit, Poeschel, Viola, Nowakowski, Grzegorz, Seymour, John F., Merli, Francesco, Haioun, Corinne, Ghesquieres, Hervé, Ziepert, Marita, Tilly, Hervé, Salles, Gilles, Shi, Qian, El‐Galaly, Tarec C., Habermann, Thomas M.
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.05.2021; Wiley Subscription Services, Inc
• Subjects: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; B-cell lymphoma; Cohort Studies; Combined Modality Therapy; Consortia; Disease Progression; Drug Resistance, Neoplasm; Early experience; Epidemiology; Female; Hematology; Humans; Immunotherapy; Kaplan-Meier Estimate; Lymphoma; Lymphoma, Large B-Cell, Diffuse - drug therapy; Lymphoma, Large B-Cell, Diffuse - mortality; Lymphoma, Large B-Cell, Diffuse - therapy; Male; Middle Aged; Mobile Applications; Models, Theoretical; Patients; Point-of-Care Systems; Prognosis; Recurrence; Risk; Severity of Illness Index; Smartphone; Treatment Outcome
• ISSN: 0361-8609; 1096-8652
• DOI: 10.1002/ajh.26149

Disease progression after frontline therapy for Diffuse large B‐cell lymphoma (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 relapsed/refractory (R/R) setting. Model building was performed in patients from the Surrogate endpoints in aggressive lymphoma (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 National Lymphoma Register (LYFO) cohorts. Model performance was assessed using time‐dependent concordance indices (c‐statistic) and calibration with metrics evaluated at 2 years from progression. Note, 1234 of 5112 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 < 0.001). 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 CAR‐T therapy as well as trial designs. The model is available in smartphone‐based point of care applications.