TY - JOUR

T1 - Relapsed / Refractory International Prognostic Index (R/R-IPI)

T2 - An international prognostic calculator for relapsed/refractory diffuse large B-cell lymphoma

AU - Maurer, Matthew J.

AU - Jakobsen, Lasse H.

AU - Mwangi, Raphael

AU - Schmitz, Norbert

AU - Farooq, Umar

AU - Flowers, Cristopher R.

AU - de Nully Brown, Peter

AU - Thompson, Carrie A.

AU - Frederiksen, Henrik

AU - Cunningham, David

AU - Jørgensen, Judit

AU - Poeschel, Viola

AU - Nowakowski, Grzegorz

AU - Seymour, John F.

AU - Merli, Francesco

AU - Haioun, Corinne

AU - Ghesquieres, Hervé

AU - Ziepert, Marita

AU - Tilly, Hervé

AU - Salles, Gilles

AU - Shi, Qian

AU - El-Galaly, Tarec C.

AU - Habermann, Thomas M.

N1 - Publisher Copyright: © 2021 Wiley Periodicals LLC.

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

U2 - 10.1002/ajh.26149

DO - 10.1002/ajh.26149

M3 - Journal article

C2 - 33661547

AN - SCOPUS:85102647795

VL - 96

SP - 599

EP - 605

JO - American Journal of Hematology

JF - American Journal of Hematology

SN - 0361-8609

IS - 5

ER -