Clinical Characteristics and Outcomes Among Very Elderly Patients with Major Lymphoma Subtypes: A Nordic Lymphoma Group Study
Authors: Wästerlid Tove , Gradel Kim , Jerkeman Mats , Frederiksen Henrik , Smedby Karin E 
Published: October 2019

Abstract
Introduction: The incidence of most lymphomas increase with age. Comorbidities, frailty and old age per se largely preclude inclusion of the very elderly in clinical trials. Thus, optimal treatment strategies and patient characteristics for elderly patients are less well defined and there is a lack of knowledge of how the oldest lymphoma patients are treated and fare. Lymphomas have a heterogeneous biology and even milder treatment may sometimes result in remission, survival benefits, and good palliation. With the rise in incidence and prevalence of lymphoma in an increasingly ageing population, improved knowledge regarding disease course, treatment and prognosis of lymphoma subtypes among the very elderly lymphoma population is warranted. Therefore, we aimed to characterise the cohort of very elderly (aged ≥85) patients with lymphoma with regard to distribution of lymphoma subtypes, choice of active treatment and overall survival (OS).
Methods: The study population was identified via the Swedish lymphoma register (SLR, >95% national coverage). Data regarding stage, prognostic factors, treatment and survival among all patients aged ≥85 diagnosed with malignant lymphomas (any histology) 2007-2013 was retrieved. Diffuse large B-cell lymphoma (DLBCL), T-cell lymphomas, Hodgkin lymphoma and mantle cell lymphoma were grouped as aggressive lymphomas. Follicular lymphoma, marginal zone lymphoma and Mb Waldenström were grouped as indolent lymphomas. Overall survival (OS) proportions were computed and illustrated using the Kaplan-Meier method. Multivariate cox regression analysis was used to investigate associations of active treatment, age, Ann Arbor stage, performance status (PS) and elevated lactate dehydrogenase (LDH) with survival.
Results: During the time period 1191 patients aged ≥85 were identified through the SLR. Of these, 298 (25%) were aged ≥90. The most commonly occurring lymphoma subtype was DLBCL (n=458, 38%). The number and proportion of patients with other subtypes are presented in Table 1. Among all patients, 36% presented with elevated LDH, 39% with PS score >2, 49% with Ann Arbor stage III-IV, 11% with bulky disease and 25% presented with B-symptoms. All these factors were associated with inferior outcome, as expected.
Data regarding administration of active treatment was available for 75% (n= 887) of patients. Among patients with aggressive lymphoma subtypes, 389 patients (72%) received active treatment, of which 44% was specified as administered with curative intent. The most common type of treatment in this group was dose reduced R-CHOP. Among patients with indolent subtypes 124 patients (49%) received active treatment (most commonly chlorambucil, bendamustine or trofosfamide). Two-year OS for patients with aggressive and indolent lymphomas was 27.5% and 58.7%, respectively. OS rates for specific subtypes are presented in table 1 and figure 1. The increase in OS associated with administration of active treatment was more prominent among patients with aggressive lymphomas. Here, patients who received active treatment had a 2-year OS rate of 36.2%, compared to 11.3% for those who did not (adjusted hazard ratio (HR): 0.47 (0.35-0.63) p=<0.0001). Among patients with indolent lymphomas 2-year OS with active treatment was 63.4% and 57.3% without, adjusted HR: 0.76 (0.5-1.1) p=0.17).
Conclusion: We demonstrate relatively encouraging overall survival data for very elderly patients from a real-world setting. Our data indicate that active treatment may be feasible also for some of the very elderly patients with lymphoma, especially among patients with aggressive lymphomas such as DLBCL. This study represents the largest cohort of its kind and this type of population based data may be useful to inform and improve clinical lymphoma management in this age group. Updated data including relative survival, comorbidity and addition of patients aged ≥85 from the Danish lymphoma register will be available and presented by the time of the ASH meeting.

Disclosures
Smedby: Janssen Pharmaceuticals: Other: The Department have recieved partial funding from Janssen Pharmaceuticals.