Real-world outcomes, access, and role of autologous stem cell transplantation in relapsed/refractory diffuse large B-cell lymphoma among AYAs and non-AYAs: A multicenter study from Peru

Abstract

Abstract Introduction: Relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) continues to pose a significant clinical challenge, despite advancements in therapeutic interventions. Autologous stem cell transplantation (ASCT) remains a standard treatment option for eligible patients; however, access to this therapy and real-world survival outcomes in Latin American countries, particularly in Peru, have not been adequately assessed. This study aims to evaluate overall survival (OS) in patients with R/R DLBCL treated at three major Peruvian centers, with a specific focus on comparing outcomes between adolescents and young adults (AYAs; 15–39 years) and older patients. Additionally, we assess the outcomes when ASCT is performed, providing real-world insights into its effectiveness and accessibility within this population.Methods: An observational retrospective, multicenter cohort study was conducted involving patients (≥15 years) diagnosed with R/R DLBCL between 2011 and 2024 at three academic centers in Peru. Primary refractory DLBCL included no response (stable disease [SD]) or progressive disease (PD) during, or by the end of frontline (EOT) immunochemotherapy (IC); partial response(PR) at the EOT ; or relapse within 3 to 12 months after achieving complete remission (CR) at EOT (early relapse). Late relapse was defined as relapse occurring more than 12 months after achieving CR. OS was defined as the time from diagnosis to death from any cause. OS was evaluated using Kaplan-Meier curves to visualize the survival probability over time for the different subgroups. Statistical significance was quantified using the log-rank test, with a significance level of 0.05. Results: A total of 233 patients were included in the final analysis. The median age was 59 years (range: 20–88). The majority (87%) belonged to the non-AYA group, 57% were male, and 58% presented stage III-IV and B symptoms. Histologically, DLBCL-NOS accounted for 54% of cases, followed by non-GCB (21%) and GCB (25%) subtypes. R-CHOP was the most commonly usedfront line IC regimen (49%). Of the patients, 67% had primary refractory disease, and 33% experienced late relapse. A total of190 received second line(2L) Pre-ASCT. The most common 2L regimen was R-ESHAP (46%), followed by R-ICE (16%). The overall response rate (ORR) at EOT for 2L was 40% (PD), 28% (PR), 25% (CR), and 7% (SD). Overall, 15 patients proceed to ASCT. At 5 years of follow-up, the OS for the entire cohort was 24%. The AYA group had a 5-year OS of 32% with a median OS of 14 months, compared to 22% in the non-AYA group, whose median OS was 9 months (95% CI; p = 0.14). The 5-year OS was significantly higher in the ASCT group (71%, 95% CI: 52–96%) compared to those who did not undergo ASCT (20%, 95% CI: 15–28%; p = 0.00014). Patients with late relapse had significantly better OS than those with refractory disease (40% vs. 18%, 95% CI; p = 0.00064). When analyzing survival by age group, AYAs demonstrated the highest overall survival (OS) at 32%, compared to 26% in patients aged 40–59 years, 19% in those aged 60–79 years, and 18% in patients over 80 years (p = 0.038). Conclusion: In this multicenter Peruvian cohort of patients with RRDLBCL, OS remains limited, particularly among those with primary refractory disease. However, patients who experienced late relapse and those who underwent ASCT demonstrated significantly improved outcomes. While no significant difference in OS was observed between AYAs and the broader non-AYA group, younger age was associated with better survival when compared across specific age subgroups. These findings highlight the importance of timely identification of transplant-eligible patients and the need to improve access to ASCT in resource-limited settings. Further follow-up and validation in larger, multicenter cohorts across worldwide are essential in countries with CART cells or bispecific are not available,