Large B-Cell Lymphoma in Elderly Patients: Completing Treatment Showed Impact on Overall Survival, a Real World Evidence
Authors: Wauters Victoria , Mahuad Carolina Valeria , Garate Gonzalo Martin , Vicente Reparaz Maria De Los Angeles , Aizpurua Florencia , Zerga Marta Elisa , Rodriguez-Otero Paula , Rodriguez Martina , Casali Claudia , Clavijo Manuela 
Published: December 2024

Introduction
Large B-cell lymphoma (LBCL) is the most common subtype of non-Hodgkin's lymphoma (NHL), being diffuse large B-cell lymphoma (DLBCL) the most prevalent, surranding 25% of NHL cases. The median age at diagnosis is 66 years, with approximately 30% of patients being older than 75 years (1).
It is known that overall survival (OS) in older patients is poorer compared to younger patients (2). Chronological age alone has proven to be one of the most significant prognostic factors, as reflected in the international prognostic index (IPI) (3). The inferior outcomes in older patients are likely attributable to multiple factors, including comorbidities, increased toxicity and lower treatment intensity (1).
Objectives
The primary outcome of this study was to assess OS in eldery patients in a private hospital in Buenos Aires, Argentina.
As secondary outcomes, we aimed to describe the treatment administrated, evaluate the response rate and adverse events, as well as to explore independent factors that might influence OS.
Methods
All patients aged ≥ 60 years diagnosed with LBCL from January 2010 to January 2024 were included. A survival analysis was performed adjusting for relevant covariates. A descriptive analysis was conducted to characterize the population, treatment regimens used and treatment-related adverse events (AE). A subgroup analysis of patients over 75 was performed.
Results
A total of 78 patients were included, with a mean follow-up of 34.81 months (SD 35.75). The mean age was 75.73 years (SD 8.55), with 44 (56%) being 75 years old or older.
Advanced stages (III or IV) were diagnosed In 60 patients (76%), 46 (58.9%) had high-intermediate or high IPI score, 26 (33.3%) had a performance status (PS) ≥ 2, and 44.9% had involvement of ≥ 2 extranodal sites.
All patients received antilymphoma treatment: 55 patients (74.6%) were treated with full-dose immunochemotherapy, 13 (17.6%) received reduced-doses and 6 (8.1%) received only Rituximab (R)-corticoids or corticosteroid monotherapy. Among those 75 years old or older, 26 (59.1%), 12 (27.3%), and 6 (13.6%) received full doses, reduced doses, and R-corticoids or corticosteroid monotherapy, respectively.
Serious AEs were seen in 35 patients (46.1%), with febrile neutropenia being the most frequent (30 patients, 39.0%).
Seventy-four patients were included in the survival analysis (4 excluded due to missing data). The OS rate at 2 years was 65.2% (95% CI 54.4-78.2%), and at 5 years, it was 50% (95% CI 37.7-66.3%). The median OS was 58.4 months (95% CI 33.1 - not reached). The most frequent cause of death was lymphoma, followed by infections.
On multivariate analysis, a PS ≥ 2 and complete treatment showed a statistically significant association with OS (HR 4.74 [CI 95% 1.65-13.59] and 0.15 [CI 95% 0.05-0.43], respectively). In the subgroup of patients older than 75 years, these variables maintained association. In this subpopulation, receiving reduced-dose treatment tended to improve OS compared to full doses (HR 0.29, CI 95% 0.04-1.89).
Conclusions
We found that OS in our population of elderly patients with LCGB is comparable to reported in the literature. We identified PS ≥ 2 as a negative factor and complete treatment as a protective factor associated with OS with a trend to improve OS in those older than 75 years old who received reduced doses of treatment.
Being a retrospective study, it was not possible to perform a comprehensive geriatric assessment that could have guided the decision to administer full or reduced doses of treatment. However, these results suggest that completing treatment, even if initiated at reduced doses positively impacts OS.
This study has certain limitations. its retrospective nature may introduce potential issues with data precision and selection bias. Although the planned sample size was reached, it was not specifically calculated for association analysis, which limits the power to establish definitive associations.
1. Tavares A, Moreira I. Diffuse large B-cell lymphoma in very elderly patients: Towards best tailored treatment-A systematic review. Crit Rev Oncol Hematol. 2021;160:103294.
2. Howlader N, et al. SEER cancer statistics review, 1975-2017. Natl Cancer Inst. 2020;4.
3. Sonnevi K, et al. Survival of very elderly patients with diffuse large B-cell lymphoma according to treatment intensity in the immunochemotherapy era: a Swedish Lymphoma Register study. Br J Haematol. 2021;192(1):75-81.