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

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 Jorgensen; Viola Poeschel; Grzegorz Nowakowski; John F. Seymour; Francesco Merli; Corinne Haioun; Herve Ghesquieres; Marita Ziepert; Herve Tilly; Gilles Salles; Qian Shi; Tarec C. El-Galaly; Thomas M. Habermann

doi:10.1002/ajh.26149

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

Journal article

Peer reviewed

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

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, …

American journal of hematology, Vol.96(5), pp.599-605

05/01/2021

DOI: 10.1002/ajh.26149

PMCID: PMC8763015

PMID: 33661547

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Abstract

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.

Hematology

Life Sciences & Biomedicine

Science & Technology

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Title: Subtitle: Relapsed / Refractory International Prognostic Index (R/R-IPI): An international prognostic calculator for relapsed/refractory diffuse large B-cell lymphoma
Creators: Matthew J. Maurer - Mayo Clin, Dept Quantitat Hlth Sci, 200 First St SW, Rochester, MN 55905 USA
Lasse H. Jakobsen - Aalborg University Hospital
Raphael Mwangi - Mayo Clinic Rochester, MN
Norbert Schmitz - University of Münster
Umar Farooq - University of Iowa
Cristopher R. Flowers - The University of Texas MD Anderson Cancer Center
Peter de Nully Brown - Copenhagen University Hospital
Carrie A. Thompson - Mayo Clinic
Henrik Frederiksen - Odense University Hospital
David Cunningham - Royal Marsden NHS Foundation Trust
Judit Jorgensen - Aarhus University
Viola Poeschel - Saarland University
Grzegorz Nowakowski - Mayo Clinic
John F. Seymour - Peter MacCallum Cancer Centre
Francesco Merli - Azienda Sanitaria Unità Locale di Reggio Emilia
Corinne Haioun - Hôpitaux Universitaires Henri-Mondor
Herve Ghesquieres - Hospices Civils de Lyon
Marita Ziepert - Leipzig University
Herve Tilly - Université de Rouen Normandie
Gilles Salles - Memorial Sloan Kettering Cancer Center
Qian Shi - Mayo Clinic
Tarec C. El-Galaly - Aalborg University Hospital
Thomas M. Habermann - Mayo Clinic
Resource Type: Journal article
Publication Details: American journal of hematology, Vol.96(5), pp.599-605
DOI: 10.1002/ajh.26149
PMID: 33661547
PMCID: PMC8763015
NLM abbreviation: Am J Hematol
ISSN: 0361-8609
eISSN: 1096-8652
Publisher: Wiley
Number of pages: 7
Grant note: U01CA195568 / National Cancer Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) P50CA097274 / University of Iowa/Mayo Clinic SPORE
Language: English
Date published: 05/01/2021
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Biostatistics; Internal Medicine
Record Identifier: 9984359584602771

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