INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) accounts for approximately 30–40% of non-Hodgkin lymphomas in adults. In older patients, treatment with full-dose R-CHOP is often limited by age-related frailty, comorbidities, and reduced tolerance to chemotherapy. R-miniCHOP, a reduced-intensity regimen, was developed to balance efficacy and safety in this population, but data comparing its real-world effectiveness to standard R-CHOP in Latin America (LATAM) remain limited.

OBJECTIVE: To compare overall survival (OS) between elderly patients with DLBCL treated with R-miniCHOP versus standard R-CHOP using real-world data from the Grupo de Estudio Latinoamericano en Linfoproliferativos (GELL) registry.

METHODS: This retrospective multicenter cohort included consecutiveness patients aged ≥65 years with newly diagnosed, histologically confirmed DLBCL treated with R-CHOP or R-miniCHOP between 2012–2017. Patients were excluded if baseline or follow-up data were incomplete. Propensity score matching (PSM) at a 3:1 ratio without caliper was performed based on age, sex, ECOG performance status, Ann Arbor stage, extranodal involvement, IPI score, and serum albumin. Missing data were imputed using a Random Forest algorithm. Post-matching balance was assessed using standardized mean differences (SMD < 0.1). OS was calculated using Kaplan–Meier curves and Cox regression. Follow-up completeness was estimated with reverse Kaplan–Meier. A subgroup analysis was conducted in patients aged >80 years. A sensitivity analysis using caliper = 0.2 was performed to confirm robustness.

RESULTS: Of 482 eligible patients (421 R-CHOP; 61 R-miniCHOP), 244 remained post-matching (183 R-CHOP; 61 R-miniCHOP). Median follow-up was 30 months. Baseline covariates were well balanced after matching (all SMD < 0.1). The mean age was 76.1 years in both groups (p = 0.679), with similar distributions in sex (47.5% vs. 45.4% male), ECOG >2 (32.8% vs. 33.3%), advanced clinical stage III–IV (65.6% vs. 65.0%), elevated LDH (47.5% vs. 48.6%), extranodal involvement (27.9% vs. 29.5%), and high-risk IPI (60.7% vs. 60.1%). Serum albumin levels were also comparable between R-miniCHOP and R-CHOP groups. At 24 months, OS was 57.1% (95% CI: 48.8–66.9%) for patients treated with R-CHOP and 56.3% (95% CI: 45.0–70.5%) for those receiving R-miniCHOP. No significant difference in OS was observed (HR: 0.96; 95% CI: 0.66–1.59; p = 0.899). Among patients aged >80 years, 1-year OS was 60.0% with R-CHOP vs. 48.6% with R-miniCHOP; no statistically significant differences were found (HR: 1.35; 95% CI: 0.56–3.24; p = 0.504). Complete response was observed in 59.0% of R-miniCHOP patients and 59.0% of R-CHOP patients post-matching; partial responses occurred in 9.8% and 8.2%, respectively. Disease progression was reported in 24.6% of R-miniCHOP vs. 29.0% of R-CHOP patients. No significant differences were found across response categories (p = 0.832). Sensitivity analysis using caliper matching confirmed the robustness of results (HR: 0.98; 95% CI: 0.62–1.54; p = 0.929), with consistent survival estimates and covariate balance.

CONCLUSION: In this multicenter real-world LATAM cohort, R-miniCHOP demonstrated comparable OS to standard R-CHOP in elderly patients with DLBCL, including those aged >80 years. These results support the use of R-miniCHOP as a viable frontline alternative for frail or very elderly patients in routine clinical practice, especially in resource-constrained health systems. However, prospective studies incorporating frailty assessments, quality-of-life, and toxicity outcomes are warranted to guide individualized treatment strategies in older adults with DLBCL.

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