Management Strategies and Outcomes for Very Elderly Patients with Diffuse Large B-Cell Lymphoma (DLBCL)
Authors: Chihara Dai , Ahmed Mohamed Amin , Oki Yasuhiro , Westin Jason R , Hagemeister Fredrick B. , Romaguera Jorge E. , Fanale Michelle A. , Lee Hun Ju , Turturro Francesco , Samaniego Felipe , Neelapu Sattva S. , Rodriguez Alma , Fowler Nathan , Wang Michael , Fayad Luis E. , Davis Richard Eric , Nastoupil Loretta 
Published: October 2019

Abstract
Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma. As the incidence of DLBCL increases with age, the number of elderly patients with DLBCL in our aging society continues to increase. However, patients aged ≥ 80 years old are often frail and carry multiple comorbidities, and are generally underrepresented in prospective clinical trials.
Patients and Methods: 207 patients, age ≥80 years of age at diagnosis of de novo DLBCL were identified between 2002 and 2014 at MD Anderson Cancer Center and included in this retrospective analysis. Failure-free survival (FFS) and overall survival (OS) were examined; baseline characteristics and frontline therapy were evaluated for the association with survival outcomes by hazard ratio (HR).
Results: Median age was 83 years (range 80-96). Fifty-five percent of the patients were male, 66% had advanced stage and 37% had poor performance status (ECOG PS≥2). Forty-five percent of the patients were IPI high-intermediate or high risk. Eighty patients (39%) were GCB and 49 patients (24%) were non-GCB subtype, respectively, according to the Hans criteria, with 78 patients lacking data for classification. Thirty-two patients (15%) had ≥4 scores by Charlson comorbidity index (CCI, Charlson 1987). Treatment received included R-CHOP (n=144, 70%), R-EPOCH (n=12, 6%), and non-anthracycline based therapies including R-CEOP and R-CVP (n=20, 10%). Sixteen patients (8%) did not receive any treatment due to deteriorated condition or patient's decision. Fifteen patients received other treatment such as radiation and rituximab monotherapy. With a median follow up of 38.1 months, 88 patients (43%) experienced progression/relapse and 123 patients (59%) died. Sixty-two patients (50%) died of lymphoma, 32 patients (26%) died of other co-morbid conditions while in remission and 17 patients (14%) died as a result of treatment complication during frontline therapy. Thirteen patients died during R-CHOP, 2 patients each died during R-CEOP or R-CVP and R-EPOCH, respectively, most were the result of infection or multi-organ failure. The 3-year FFS and OS were 55% and 54%, respectively. After 3-years, almost all deaths were attributed to other diseases (Figure A). Patients who received R-CHOP or R-EPOCH had a significantly longer FFS than patients who received R-CEOP or R-CVP (Figure B). CCI ≥4 was not associated with inferior FFS but was significantly associated with inferior OS. Multivariate analysis for OS adjusted by IPI and frontline treatment revealed that being female was associated with significantly longer OS (HR: 0.50, 95% CI, 0.33-0.75, p<0.01) and patients with beta-2 microglubulin >2.0mg/l had significantly inferior OS (HR: 7.21, 95% CI, 1.67-31.1, p=0.01).
Conclusion: Patients with DLBCL aged ≥80 years who received anthracycline-based regimens such as R-CHOP or R-EPOCH had outcomes similar to younger patients with de novo DLBCL. Although they carry higher risks of therapy-related mortality, anthracycline-based regimens are moderately well tolerated, and their use should not be minimized based solely on age. Inclusion of very elderly patients in prospective clinical trials is warranted to identify the most effective management strategy for this population.
Figure 1. Figure 1.

Disclosures
Westin: Spectrum: Research Funding. Fanale:Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Research Funding; Infinity: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Research Funding; Genentech: Research Funding; Medimmune: Research Funding; Novartis: Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Molecular Templates: Research Funding; ADC Therapeutics: Research Funding; Onyx: Research Funding; Gilead: Research Funding. Rodriguez:Orthobiotech: Research Funding. Wang:Celgene: Research Funding. Nastoupil:AbbVie: Research Funding; TG Therapeutics: Research Funding; Genentech: Honoraria; Celgene: Honoraria; Janssen: Research Funding.