Abstract
Optimizing risk stratification in patients aged 80+ years with large B-cell lymphoma: Comparison of prognostic indices in three pooled international cohorts
Blood, Vol.146(Supplement), pp.786-786
11/03/2025
DOI: 10.1182/blood-2025-786
Abstract
Introduction The International Prognostic Index (IPI) is widely used to stratify risk in large B-cell lymphoma (LBCL) across all ages, with age-adjusted (aa)IPI applied to younger patients. While there have been efforts to develop prognostic indices (PIs) tailored to older patients, few are adopted in clinical practice due to their complexity and reliance on functional assessments, which are not routinely collected in real-world registry datasets. Recently proposed SENIOR-IPI (Dubois, ASH 2024) was developed for older patients with LBCL receiving anthracycline (A)-based therapy. We assessed the performance of standard and novel PIs in patients aged 80+ years and externally validated the SENIOR-IPI.
Methods We harmonized and pooled data of patients aged 80+ years with newly diagnosed LBCL from a national registry and two prospective cohorts: NiHiL (Czech Republic, enrolled 2010–2023), LEO (USA; n=222, 2015–2020), and MER (USA; n=77, 2010–2015), forming a cohort of 819 individuals. We included 536 individuals with complete data on IPI components and albumin, including 485 treated with chemotherapy and 397 with A-based regimens (primary cohort). Following PIs were evaluated: IPI, NCCN-IPI, (aa)IPI, and SENIOR-IPI (age per year, aaIPI components, LDH >3x ULN as extra point, and albumin, all weighted six-fold; extranodal involvement excluded due to lack of prognostic significance). Multivariable hazard ratios (HR) were estimated using Cox proportional hazards models; discriminative ability was assessed using C-index and calibration plots. The primary endpoint was overall survival (OS); event-free survival results were consistent (230/357 events were deaths) and are not reported here.
Results Among the 397 A-treated patients (median age 82 years, range 80–99), ECOG performance status (PS) 2–4 was observed in 35% of patients, clinical stage III–IV in 67%, elevated LDH in 65% (8% with >3x ULN), >1 extranodal (EN) site in 32%, and albumin levels < 3.5 g/dL in 27%. In multivariable modeling, only age per year (HR=1.07, P<0.01), and clinical stage (HR=1.36, P=0.048) were independent predictors of OS, whereas ECOG PS (HR=1.27, P=0.12), trichotomized LDH by ULN (HR=1.23, P=0.08) and albumin (HR=1.17, P=0.35) were not significant.
SENIOR-IPI had the highest discrimination (C-index 0.631) in A-treated patients, outperforming IPI (0.617), NCCN-IPI (0.591), and aaIPI (0.620), with consistent results across cohorts: NiHiL (0.633), LEO (0.619), and MER (0.621). SENIOR-IPI stratified patients into low- (L-Risk, 0–9 points, 28%), low-intermediate (L-Int, 10–19 points, 42%), high-intermediate (H-Int, 20–29 points, 23%), and high-risk (H-Risk, 30–40 points, 7%) categories, with OS medians of 6.3, 3.8, 2.4, and 1.4 years, respectively (P<0.01), and significant separation between L-Int and H-Int (HR=1.47, P=0.02). By comparison, IPI categorized patients as L-Risk (12%), L-Int (24%), H-Int (27%), and H-Risk (37%), with median OS of 8.7, 4.6, 4.8, and 1.9 years, resp. (P<0.01). aaIPI yielded following distributions: 13%, 29%, 37%, and 21%; and median OS: 8.7, 5.3, 3.4, and 1.5 years; P<0.01. NCCN-IPI stratified patients into three groups: L-Int (13%), H-Int (49%), and H-Risk (39%), with respective OS medians of 8.7, 4.1, and 2.5 years (P<0.01). All PIs showed modest overestimation of mortality (calibration slopes: SENIOR-IPI 1.36; IPI 1.24; aaIPI 1.30; NCCN-IPI 1.26; intercept: -0.97, -0.87, -0.92, -0.87, resp.).
In the entire cohort (n=536), SENIOR-IPI showed highest C-index (0.651 vs IPI 0.622, aaIPI 0.631, NCCN-IPI 0.606), and stratified patients into L-Risk (26%, 2-year OS: 6.4 years), L-Int (40%, 3.2 years), H-Int (24%, 1.5 years), and H-Risk (10%, 0.6 years). Calibration slope was 1.18 (intercept -0.33). Among patients not receiving chemotherapy, SENIOR-IPI also performed best (C-index 0.759 vs IPI 0.738, aaIPI 0.757, NCCN-IPI 0.728).
Conclusion SENIOR-IPI enables effective risk stratification of patients aged 80+ years with LBCL into four prognostically distinct groups, outperforming traditional indices (IPI, NCCN-IPI, aaIPI) in patients receiving A-based therapy, as well as in the entire cohort and in patients not receiving chemotherapy. While its discrimination is superior, modest miscalibration suggests that future recalibration may improve precision. These findings support SENIOR-IPI as a clinically relevant prognostic tool for the elderly LBCL patient population.
Funding: NU21-03-00411, P50 CA97274, U01 CA195568.
Details
- Title: Subtitle
- Optimizing risk stratification in patients aged 80+ years with large B-cell lymphoma: Comparison of prognostic indices in three pooled international cohorts
- Creators
- Jean Koff - Emory UniversityAlice Sykorova - University Hospital Hradec KrálovéEric Mou - University of IowaHeidi Mocikova - Charles UniversityAndrew Feldman - Mayo ClinicZuzana Prouzova - Charles UniversityBrad Kahl - Saint Louis UniversityJuraj Ďuraš - University Hospital OstravaMazie Tsang - TOCA at Banner HealthKaterina Steinerova - Charles UniversityChijioke Nze - The University of Texas MD Anderson Cancer CenterDiana Malarikova - Charles UniversityRaphael Mwangi - Mayo ClinicAndrea Janikova - Masaryk UniversityArushi Khurana - Mayo ClinicJan Galko - Charles UniversityPeter Martin - Cornell UniversityKamila Polgarova - Charles UniversitySergei Syrbu - University of IowaJan Koren - Charles UniversityAles Obr - Palacký University OlomoucJonathan Friedberg - University of Rochester Medical CenterDavid Belada - University Hospital Hradec KrálovéMichal Kascak - University Hospital OstravaJonathon Cohen - Emory UniversityMichal Masar - Charles UniversityAlexandra Suri - Charles UniversityGrzegorz Nowakowski - Mayo ClinicSamuel Hricko - Masaryk UniversityAndrea Hrušková - Palacký University OlomoucChristopher Flowers - The University of Texas MD Anderson Cancer CenterVeronika Bergerova - Charles UniversityPetra BlahovcovaProkop Vodicka - Charles UniversityMatthew Maurer - Mayo ClinicYucai Wang - Mayo ClinicJozef Michalka - Masaryk UniversityKaterina Benesova - Charles UniversityVit Campr - Charles UniversityPatrick Reagan - University of Rochester Medical CenterThomas Habermann - Mayo ClinicDavid Salek - Masaryk UniversityPavel Klener - Charles UniversityIzidore S. Lossos - Sylvester Comprehensive Cancer CenterJames Cerhan - Mayo ClinicVit Prochazka - University Hospital OlomoucMarek Trneny - Charles University
- Resource Type
- Abstract
- Publication Details
- Blood, Vol.146(Supplement), pp.786-786
- DOI
- 10.1182/blood-2025-786
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 11/03/2025
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Epidemiology; Pathology; Internal Medicine
- Record Identifier
- 9985116910902771
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