Oral Chemotherapy Application in Elderly Patients With Diffuse Large B-Cell Lymphoma: An Alternative Regimen in Retrospective Analysis

Abstract

Background A combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is considered the standard treatment for diffuse large B-cell lymphoma (DLBCL). However, no standard treatment has been established for older patients (age ≥ 75 years). This study retrospectively analyzed different treatment strategies in older patients with DLBCL with different chemotherapy regimens and compared the survival rate of patients using oral or intravenous form cyclophosphamide and etoposide in a single center. Methods We reviewed the records of older patients with DLBCL, aged ≥ 75 years, from January 2010 to August 2019. The different treatment combinations, clinical characteristics, response rates, and toxicity profiles were analyzed. The median overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier (KM) method. Cox regression model was used to identify the risk factors. Results Eighty-four patients were included. One-quarter of the patients received cytoreduction treatment because of their poor medical condition at the time of diagnosis. Twenty-six percent of the patients were aged ≥ 85 at the time of diagnosis and 46.7% completed the treatment course. Patients receiving non-anthracycline-containing (non-ACR) treatment had worse Charlson comorbidity index, worse PFS, lower body mass index, or were older. The mean anthracycline accumulative dose in the anthracycline-containing (ACR) group was 134 mg/m 2 . The median OS was 17.2 months and median PFS was 7.7 months. The PFS of R-CHOP is better than R-mini-CHOP and R-CVOP without statistical significance, but OS of R-CHOP is not better than the other regimens. Conclusion The toxicity, efficacy, and KM curve for OS and PFS in the non-ACR group were lower compared to ACR group, without statistical significance. R-CVOP had similar OS with R-mini-CHOP in our study. The result does not mean etoposide could totally substitute for anthracycline, but etoposide did have lower early progression rate (12.5%), and it may be an option for frail patients with comorbidity. Oral form cyclophosphamide and etoposide could be considered as a substitute for intravenous administration because of the similar effect and toxic profile.

Appropriate Treatment Intensity for Diffuse Large B-Cell Lymphoma in the Older Population: A Review of the Literature

“…There may thus be selection bias regarding the ineligibility for standard-dose chemotherapy because no proper randomization could be achieved. R-CHOP is not standardized for older patients with DLBCL, particularly for those aged ≥80 years [ 17 , 18 ].…”

“…Peyrade et al evaluated and recommended R-mini-CHOP as standard therapy in patients aged >80 years with DLBCL [ 28 ]. Liao et al retrospectively compared R-CHOP, R-mini-CHOP, and R-CVOP in patients aged ≥75 years and concluded that OS was comparable and differences in PFS were insignificant [ 18 ]. Verner et al undertook a phase 2 study of R-mini-CHOP plus ibrutinib in patients aged >75 years and showed that, although 2-year OS was 68%, ibrutinib was discontinued in 25% of patients, primarily because of adverse events [ 41 ].…”

“…Peyrade et al demonstrated a 2-year OS of 64.7% in patients aged >80 years with DLBCL treated with ofatumumab, pre-phase treatment (oral vincristine followed by oral prednisone), and reduced-intensity CHOP [ 29 ]. Pola-R-miniCHP [ 5 , 42 ], as well as other chemotherapy options, including R-mini-CEOP, R-split CHOP, R-CVOP, and R-GCVP [ 18 , 43 ], may also be promising therapies for older patients with DLBCL.…”