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 - © 2021 Wiley Periodicals LLC.
PY - 2021/5/1
Y1 - 2021/5/1
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.
UR - http://www.scopus.com/inward/record.url?scp=85102647795&partnerID=8YFLogxK
U2 - 10.1002/ajh.26149
DO - 10.1002/ajh.26149
M3 - Journal article
C2 - 33661547
AN - SCOPUS:85102647795
SN - 0361-8609
VL - 96
SP - 599
EP - 605
JO - American Journal of Hematology
JF - American Journal of Hematology
IS - 5
ER -