Real-world treatment and outcomes of Mantle Cell Lymphoma in Latin America: A multinational cohort analysis

Abstract

Abstract Background: Mantle cell lymphoma (MCL) is a rare, aggressive B-cell malignancy with heterogeneous clinical behavior and poor long-term outcomes. While treatment advances have significantly improved outcomes in high-income countries, little is known about how the real-world treatments and survival in LATAM. This study aims to characterize the clinical presentation, therapeutic approaches, transplantation and novel agents access, and survival outcomes in LATAM patients with MCL, and to identify country- and system-level factors contributing to variability in care. Methods This was a retrospective, multicenter cohort study conducted across 19 institutions in 8 LATAM countries between 2015 and 2024. Adult patients (≥18y) diagnosed with MCL were included when complete clinical, treatment, and outcome data were available. Variables analyzed included demographics, stage, prognostic indexes, frontline and salvage therapies, autologous stem cell transplantation (ASCT), access to targeted agents, and survival. Subgroup analyses were conducted by age (<65 vs. ≥65), country, and institution type (public vs. academic/private). Primary endpoints were overall survival (OS), progression-free survival (PFS), and treatment response. Secondary endpoints included ASCT eligibility and use, access to maintenance therapy, and uptake of second-line (2L) targeted therapies. Results A total of 222 patients met the inclusion criteria. Median age was 64 years (range, 34–89), males predominance (70.4%). At diagnosis, 72.5% of patients had stage III/IV, 66% extra nodal involvement, 62.4% bone marrow infiltration, 49.8% elevated LDH, and 54.6% showed elevated β2-microglobulin. ECOG ps ≥2 was observed in 57.9% of patients. High-risk MIPI was present 47.8% overall and significantly more common in older patients (≥65y: 69.2% vs 41.8%; p=0.001). 1L therapy varied: 43.6% received cytarabine-based regimens, 25.3% Rituximab (R)-CHOP, and 20% R-Bendamustine (RB). Patients <65y received more intensive therapy (69.2%), while those ≥65y received RB more often (37%). Public hospitals favored R-CHOP (41.2%), whereas academic/private centers preferred cytarabine-based regimens (50%). Watch&Wait was used in 9.9%. Among transplant-eligible patients, only 43.4% (n=51) underwent ASCT; main barrier was medical criteria (e.g., comorbidities, poor performance status, suboptimal response to 1L) (75%) rather than financial. R-maintenance (RM) therapy increased after 2018 from 53.3% to 63.4%. Only 19.4% of patients <65y and 27.4% of those ≥65y received RM after 1L induction chemoimmunotherapy. Among transplanted patients, the post-ASCT RM group showed lower 3-year mortality (22.6% vs 33.3%) and improved overall survival. 2L therapy was given to 34% of patients. BTKi were used 32.1%, venetoclax 3.6%, and almost exclusively in private settings. BTKi access was markedly lower in public institutions (11.9% vs. 52.4%). Countries such as Cuba, Peru, and Bolivia reported no access to targeted therapies. Most relapsed/refractory patients received chemo-based regimens, resulting in modest outcomes. Complete response (CR), partial response (PR), and progression to 2L therapy were 31.4%, 41.4%, and 27.1%, respectively. Survival analysis included 218 patients with 81 deaths. Median follow-up was 26.8 months (range: IQR 12.0-44.9). OS at 12, 24, and 36 months was 88%, 77.4%, and 68.4%, respectively. Median OS was 80.5 months (95% CI: 60.1–106.3). PFS at 12, 24, and 36 months was 72.9%, 55.1%, and 47.9%; median PFS was 29.7 months. ASCT significantly improved survival, 3-year OS 79.9% vs. 61.3%; median OS 9.9 vs. 4.5y; HR 2.7, 95% CI: 1.43–5.13, p=0.002). Conclusions This real-world LATAM cohort reveals high-risk clinical profiles at diagnosis and disparities in access to transplant, maintenance, and novel agents. While ASCT showed a clear survival benefit, its implementation remains uneven. RM, post-ASCT and in older patients, was underused despite evidence of benefit and absence of financial barriers. Access to 2L targeted therapies remains extremely limited in public institutions and absent in several countries, impacting post-relapse outcomes. Despite these gaps, survival metrics appear comparable to international cohorts, suggesting biological or demographic resilience. These findings underscore the need for equitable access, regional treatment harmonization, and expansion of clinical trial infrastructure across LATAM.