Diffuse Large B-Cell Lymphoma in the Elderly : Retrospective Analysis from a Single Tertiary Cancer Center in India
Authors: Jobanputra Kunal N. , Nayak Lingaraj , Jain Hasmukh , Sengar Dr. Manju 
Published: November 2021

Abstract
Introduction
Diffuse large B-cell lymphoma (DLBCL) commonly affects the elderly population and the treatment is often challenging because of the close interplay between age, comorbidities, frailty as well as cognitive and psychosocial factors. Anthracycline constitutes the cornerstone of the treatment regimen of Non-Hodgkin lymphoma but is associated with several side-effects including cardiotoxicity. At our institute, we replace doxorubicin with etoposide in cases where compromised cardiac function, performance status (PS) and multiple comorbidities are major concerns. We aim to retrospectively analyze the treatment outcomes of patients with DLBCL aged ≥ 60 years and specifically compare R-CHOP and R-CEOP regimens.

Methods
In this retrospective study, we included patients aged ≥ 60 years, newly diagnosed with DLBCL according to WHO classification between January 2015 to December 2018 at our center. Chemotherapy regimens received included R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone), R-CE (Etoposide) OP for anthracycline-ineligible or elderly frail patients and R-EPOCH, followed by radiotherapy for residual disease or bulky sites (size &gt; 7cm). The decision to use anthracycline or non-anthracycline based regimen was at the discretion of the physician depending on the performance status, frailty and serum albumin levels. Dose of etoposide used in the R-CEOP regimen was 65mg/m 2 orally on day 1-3. Primary G-CSF prophylaxis was used in all patients. After 4 cycles of chemotherapy, patients underwent an interim PET-CT for response evaluation. Patients who attained partial response underwent a repeat PET-CT evaluation at the end of 6 cycles. Post treatment completion, patients were followed up for clinical examination every three months for the first two years, six monthly for the next three years and annually thereafter.

Results
A total of 218 patients were included. The median age of patients was 65 years (range, 60-88 years). Patients were divided into two age-groups with 124 patients (56.9%) of the age group of 60-65 years and 94 patients (43.1%) were aged above 65 years. Of the 218 patients, 71 patients (32.6%) received R-CHOP regimen and 137 patients (62.4%) received R-CEOP regimen, while 10 patients (5.0%) received R-EPOCH. More patients aged &gt;65 years received R-CEOP than in the 60-65 years age group (83% vs 47.6%) and the difference was statistically significant (p-value &lt;0.001). Reasons for replacing doxorubicin were cardiac contraindications (9.6%), presence of hypertension or ≥ 2 significant comorbidities (29.9%), advanced age (age ≥ 75 years, 8.0%), baseline Eastern Cooperative Oncology Group (ECOG) PS of &gt; 2 (3.6%), and physician's discretion in 48.9% of cases. Baseline disease characteristics including NCCN-IPI of patients treated with both these regimens were comparable. Complete response rate and overall response rate were higher in the R-CHOP group compared to the R-CEOP group, but statistically significant difference was found only among 60-65 years of age group. Among patients aged 60-65 years, the incidence of febrile neutropenia and grade III/IV hematological toxicities were significantly higher in the R-CHOP group than in the R-CEOP group. The overall median follow-up was 22.71 months (Range 1-81 months). The 2-year progression-free survival (PFS) rate in the R-CHOP group was higher than that in the R-CEOP group (79.1% vs 49.6%, p-value &lt;0.001) (Figure 1). This statistically higher 2-year PFS rate was found among patients with early as well as advanced stage disease, and also in the age group of 60-65 years (Figure 2, 3). Match pairing analysis after adjusting for confounders like NCCN-IPI and presence of bulky disease showed significantly higher 2-year PFS rate in the R-CHOP group than in the R-CEOP group (70.0% vs 34.6%, p-value &lt;0.001). ECOG PS at presentation, NCCN-IPI and the chemotherapy regimen were found to be significant factors for PFS by multivariate analysis (Table 1).

Conclusion
Age and comorbidities are not absolute contraindications to the use of anthracyclines. Fit patients without cardiac contraindications should receive R-CHOP regimen whenever possible. Geriatric assessment tools should be used for the frail or unfit patients to guide appropriate therapy and further prospective trials should be done in this direction.

Figure 1 Figure 1.

Disclosures
No relevant conflicts of interest to declare.