Polatuzumab-vedotin in large diffuse B-cell lymphoma: A multicenter observational study from Latin America (2020–2024)

Abstract Introduction: Polatuzumab vedotin (Pola), an anti-CD79b antibody-drug conjugate linked to monomethyl auristatin E (MMAE), demonstrated improved progression-free survival (PFS) in the phase 3 POLARIX trial when combined with rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) compared with R-CHOP in the frontline treatment of diffuse large B-cell lymphoma (DLBCL) (Sehn et al., 2022). However, real-world data on the clinical characteristics and outcomes of patients receiving Pola-based regimens in Latin America remain scarce. This study aimed to characterize the clinical profile, treatment patterns, and outcomes of patients with DLBCL treated with Pola-based regimens in a real-world, resource-constrained setting. Methods: We conducted a multicenter, retrospective observational study including adult patients with DLBCL treated with Pola-based regimens at Fundación Santa Fe de Bogotá, Clínica Las Américas, and Instituto Alexander Fleming from 2020 onward. Data were extracted from electronic medical records. Descriptive statistics were used to summarize patient characteristics. The primary outcome was response rate, assessed based on physician documentation and stratified by line of therapy. Results: A total of 25 patients were included. The median age was 61 years (SD: 11.86), and 65.4% (n = 17) were male. Racial distribution varied by site: all Argentine patients were classified as Caucasian (30.8%, n = 8), while among Colombian patients, 34.6% (n = 9) were mixed-race, 15.4% (n = 4) Caucasian, and 19.2% (n = 5) had missing data. Most patients presented with advanced-stage disease (stage IV: 69.2%, n = 18). IPI scores were most frequently intermediate-high and high (26.9%, n = 7 each). The germinal center B-cell (GCB) subtype was most common (56%, n = 14), and ECOG ≥2 was reported in 42.3%—notably higher than in POLARIX (15%) (Tilly et al., 2022). CD79b expression was positive in 20% (n = 3), and TP53 was positive in 5% (n = 1) by immunohistochemistry. FISH analysis revealed BCL2/MYC rearrangements in 26.3% (n = 5) and triple-hit (BCL2/MYC/BCL6) in 11.7% (n = 2). Response rates were stratified by line of therapy. Among patients receiving Pola in the first-line setting (n = 2), both achieved a complete response (CR). In the second-line setting (n = 12), 5 achieved CR, 1 had stable disease (SD), 3 progressed, and 3 had pending assessments. In third-line or beyond (n = 11), 5 achieved CR, 2 had a partial response (PR), 3 progressed, and 1 had not yet been assessed. These findings suggest Pola retains clinical activity across multiple treatment lines. These real-world responses are comparable to published data, where pola+BR yields ORR ~62.5% and CR 40% in R/R DLBCL (Sehn et al., 2022). Survival analysis excluded the 2 first-line patients to standardize findings to those who received ≥2 lines of therapy. At a median follow-up of 2 years, estimated 1-year overall survival (OS) was 81.6% (95% CI: 53.0–93.7%), with 3- and 5-year OS plateauing at 39.9% (95% CI: 13.7–65.4%). Patients with high-risk IPI had significantly worse OS (p = 0.0096). No statistically significant association was found between biomarker-defined subgroups and OS (p = 0.21). Compared with real-world cohorts in relapsed/refractory (R/R) DLBCL—which report median OS of 9 months and CR rates of ~18.2% (Argnani et al., 2022)—our third- and fourth-line results were consistent. Conclusions: To our knowledge, this is one of the first real-world analyses of polatuzumab vedotin (Pola)-based regimens in Latin America. In a resource-constrained setting with heterogeneous treatment strategies, Pola demonstrated meaningful clinical activity across multiple lines of therapy. Response rates and 1-year overall survival were comparable to those reported in the phase 2 trial by (Sehn et al.,2022) and exceeded outcomes from other real-world cohorts in relapsed/refractory DLBCL. Importantly, our findings support the early integration of Pola, particularly in high-risk or non-GCB DLBCL, where its benefit may be maximized. The IPI retained prognostic significance, highlighting its utility even in biomarker-diverse populations. Larger prospective studies are needed to validate these observations and expand access to novel therapies in underrepresented regions.