Unveiling the Burden of Diffuse Large B Cell Lymphoma in Paraguay: A Multicenter Study on Clinical Outcomes and Diagnostic Access

Introduction Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, comprising 30-40% of cases, and with overall survival rates of up to 64% at 10 years. DLBCL is biologically diverse, with two main molecular subtypes: germinal center B-cell (GCB) and activated B-cell (ABC). The GCB subtype typically shows better outcomes and higher response rates to R-CHOP therapy. In contrast, the ABC subtype has a poorer prognosis but responds better to novel agents like ibrutinib and lenalidomide. Despite advances in DLBCL biology and treatment, disparities in access to care and diagnostics persist, especially in low- and middle-income countries. In Paraguay, limited data exist on DLBCL, with no comprehensive characterization of its clinical and molecular profiles, treatment patterns, or outcomes. This study aims to address these gaps by analyzing patients (pts) with newly diagnosed DLBCL managed at large referral centers. Methods We conducted a retrospective cohort study of pts aged ≥18 years with newly diagnosed DLBCL between 2015-2023 across 3 academic centers in Paraguay. Patient data were manually extracted from medical records on a standardized form. Primary endpoint was overall survival (OS) defined as time from diagnosis to death from any cause, while secondary endpoint was progression-free survival (PFS) defined as time from diagnosis to relapse, disease progression or death from any cause. Kaplan-Meier and Log-rank tests were used to estimate and compare survival probabilities. Results A total of 134 pts were included. The median age at diagnosis was 60 years (52% >60 years; range 18-93), with a male predominance (60%). Most pts (74%) had advanced stage (stages III-IV) disease, presented B symptoms (57%) and had ECOG performance status of ≤1 (69%) at debut. Only 17 pts (13%) underwent FISH testing, with the cost borne by the pts as it is not covered by public health insurance or social security. DLBCL subtypes were evaluated in all pts with GCB phenotype in 55% and non-GCB in 45% of cases. Baseline PET/CT scanning was performed in 56% and at the end of treatment PET/CT in 72% of pts. The most frequently used regimen was CHOP-like therapy with 91% receiving it in combination with rituximab (6% received R-mini-CHOP) and 2% without rituximab; 5% of pts received other less intensive regimens without anthracyclines and 2% received the intensified regimen dose-adjusted R-EPOCH. Intrathecal methotrexate prophylaxis was given to 4% of pts. With a median follow-up of 36 months (29-40), the 3-year OS and PFS rates for all pts were 83% and 68%, respectively. ECOG of ≤1 was associated to improved OS and PFS (90% vs 75%, p=0.02; and 81% vs 49% p<0.001; respectively). Pts with GCB DLBCL had better OS and PFS rates than pts with non-CG DLBCL (90% vs 72%, p=0.02; and 80% vs 55% p=0.006; respectively). We were able to validate with R-IPI, however, the NCCN-IPI was not able to discriminate high from low risk groups. Lastly, there were no differences in survival outcomes based on age (≥60 vs <60), sex, presence of B symptoms, and cancer stage (localized vs advanced), the latter likely related to the low number of pts with localized stage disease. Conclusion To our knowledge, this is the first multicenter study to comprehensively characterize the clinical features and outcomes of pts with DLBCL in Paraguay. Our findings highlight significant diagnostic and therapeutic challenges, particularly the limited access to essential staging tools like PET/CT and FISH testing. Despite these challenges, our cohort demonstrated survival outcomes that align with international standards. Nonetheless, disparities in outcomes were observed based on molecular subtypes, with GCB pts showing better survival rates than non-GCB pts, underscoring the biological heterogeneity of DLBCL. The study also revealed the lack of significant survival differences based on age, sex, B symptoms, and cancer stage, likely reflecting the advanced stage at diagnosis in most pts and the homogeneity in treatment regimens. These findings emphasize the urgent need for improved healthcare infrastructure and access to advanced diagnostic tools in Paraguay. Enhancing diagnostic capabilities could enable better risk stratification and treatment personalization, ultimately improving outcomes for DLBCL pts in resource-limited settings