Clinical Characteristics and Outcomes of Elderly Patients with Stage I Diffuse Large B-Cell Lymphoma: A Study By Jiangsu Cooperative Lymphoma Group (JCLG)
Authors: Shi Wenyu , Xia Yi , Li Yongle , Zhou Jiahao , He Jing , Gu Weiying , Li Bingzong , Jia Tao , Lu Tingxun , Liu Ping , Cheng Yue-Xin , Miao Yuqing , Xie Xiaoyan , Zhang Yunping , Lu Xuzhang , Wang Chunling , Xu Min , Shi Jinning , Chen Weifeng , Zhuang Wanchuan , Qian Zhen , Ni Haiwen , Chen Yifei , Li Jianyong 
Published: December 2023

Introduction
Stage I diffuse large B-cell lymphoma (DLBCL) is defined as the involvement of a single lymph node or a group of adjacent nodes, or the presence of isolated extranodal lesions without nodal involvement. Generally, the prognosis of stage I DLBCL is excellent with 5-year overall survival (OS) over 90%. However, differences in disease characteristics and prognosis between elderly and younger patients with stage I DLBCL were not clear.
Methods
In this study, we conducted a retrospective data collection from 255 newly diagnosed patients with stage I DLBCL who were above 60 years old. The data was collected from 19 medical centers of of Jiangsu Cooperative Lymphoma Group (JCLG) located in Jiangsu Province, China. To enroll, patients had to undergo staging using either positron emission tomography/computed tomography (PET/CT) or contrast-enhanced CT scans of the chest, abdomen, and pelvis (C/A/P CT) with contrast, as well as bone marrow examination.
Results
The clinical characteristics of the 255 patients are presented in Table 1. The median age at presentation was 69 years, with a range of 61 to 92 years old. Among the 255 patients, 65.9% had at least one coexistent disease. A high Charlson Comorbidity Index (CCI), defined as ≥2, was found in 10.1% of patients. 63.9% had extranodal disease. The most common sites of extranodal involvement were the stomach (37.4%), intestine (19.0%), testes (11%), breast (7.4%), skin/soft tissue (5.5%), and sinus/nose (5.5%). According to the Hans algorithm, the non-GCB subtype accounted for 63.7% of patients and did not show a significant difference between the nodal and extranodal groups. None of the patients were diagnosed with double-hit lymphoma. Additionally, EBER was found to be positive in 3.7% of patients (5/134).
The treatment approaches are outlined in Table 1. A total of 84.5% patients received the R-CHOP regimen as their primary treatment. The median number of R-CHOP courses administered was 6. Among the 204 patients with treatment evaluation records, 183 (89.7%) achieved complete remission (CR).
With a median follow-up time of 30 months, 32 patients died during the follow-up period. Among them, 18 died from causes unrelated to lymphoma at a median age of 73 years. The 3-year progression-free survival (PFS) rate was 81.5% and the 3-year OS rate was 85.6%. In the univariate analysis, age ≥75 years (HR 3.30, P &lt; 0·001) and CCI ≥2 (HR 2.92, P = 0·002) were significantly associated with worse PFS; age ≥75 years (HR 3·29, P = 0·001), CCI ≥2 (HR 2.57, P = 0·022) and non-GCB subtype (HR 1.79, P = 0·018) were significantly associated with worse OS. In multivariate analysis, age ≥75 years (HR 2.91, P = 0·001) and CCI ≥2 (HR 2.32, P = 0·02) remained independent risk indicators for worse PFS; age ≥75 years (HR 2.57, P = 0·015) and non-GCB subtype (HR 1.74, P = 0·025) were independent risk indicators for worse OS. None of the prognostic models including IPI, NCCN-IPI or stage-modified International Prognostic Index (sm-IPI) demonstrated statistical significance. However, by incorporating age≥75 and CCI≥2 into the sm-IPI, we could be able to provide a more accurate prediction of the prognosis for elderly patients with stage I DLBCL (Figure 1).
Relapse occurred in 20 patients at a median time of 9 months. 91.7% (11/12) of patients with early relapse (defined as PFS less than 24 months) experienced recurrence in the same anatomical site as the primary disease. In contrast, only 25% (2/8) of patients with late relapse exhibited relapse in the initial site.
Conclusion
To the best of our knowledge, this is the largest retrospective study conducted specifically on stage I DLBCL in the Asian population during the rituximab era. Our findings suggest that elderly patients with stage I DLBCL have a higher non-lymphoma-related mortality rate and a higher likelihood of relapse in the same anatomical site for early relapses compared to late relapses. Integrating age ≥75 and CCI score into the sm-IPI will help to better assess prognosis.