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. 2021 May 1;96(5):599-605.
doi: 10.1002/ajh.26149. Epub 2021 Mar 18.

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

Matthew J Maurer  1 , Lasse H Jakobsen  2 , Raphael Mwangi  1 , Norbert Schmitz  3 , Umar Farooq  4 , Cristopher R Flowers  5 , Peter de Nully Brown  6 , Carrie A Thompson  7 , Henrik Frederiksen  8 , David Cunningham  9 , Judit Jørgensen  10 , Viola Poeschel  11 , Grzegorz Nowakowski  7 , John F Seymour  12 , Francesco Merli  13 , Corinne Haioun  14 , Hervé Ghesquieres  15 , Marita Ziepert  16 , Hervé Tilly  17 , Gilles Salles  18 , Qian Shi  1 , Tarec C El-Galaly  2 , Thomas M Habermann  7
Affiliations

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

Matthew J Maurer et al. Am J Hematol. .

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.

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Conflict of interest statement

Disclosures:

Maurer: research funding from Nanostring, Celgene, Morphosys, Genentech and advisory board/consulting from Kite, Pfizer, Morphosys; Farooq: honoraria from Kite; Brown: advisory board from BMS, Incyte, Roche, Takeda; Cunningham: research funding from Amgen, Sanofi, Merrimack, AstraZeneca, Celgene, MedImmune, Bayer, 4SC, Clovis, Eli Lilly, Jannsen, Merck; Jorgensen: advisory board from Gilead, Novartis, Roche, BMS; Poeschel: travel grants from Abbvie, Amgen, and Roche; Tilly personal fees and non-financial support from Roche, personal fees from Karyopharm, AstraZeneca, BMS, Servier, Janssen-Cilag; El-Galaly: employment by Roche. All remaining authors have declared no conflicts of interest.

Figures

Figure 1:
Figure 1:
(A) Kaplan Meier Curve of Overall Survival from First Progression by Time to Progression (Months) on Frontline Immunochemotherapy (IC) in SEAL Cohort. (B) Functional Form of the Association Between Time to Progression on IC (Continuous Months) and Overall Survival in SEAL Cohort (C) Kaplan Meier Curve of Overall Survival from First Progression by Age at Progression in SEAL Cohort. (D) Functional Form of the Association Between Age at Progression (Continuous Years) and Overall Survival in SEAL Cohort
Figure 2:
Figure 2:
Nomogram for the R/R IPI Model
Figure 3:
Figure 3:
Calibration Curve (A) SEAL Cohort (Discovery) (B) LYFO Cohort (Validation) (C) MER Cohort (Validation)
See this image and copyright information in PMC

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