Abstract
Background: The GALLIUM trial established obinutuzumab-based immunochemotherapy as a new standard of care in first-line treatment for patients with advanced follicular lymphoma (FL), demonstrating a superior progression-free survival (PFS) and a lower cumulative rate of progression of disease within 24 months from treatment initiation (POD24) compared to rituximab-based regimens (Marcus et al., NEJM 2017; Seymour et al., Hematol 2018). The URBAN study (ML41215; NCT04034056) is a non-interventional, ambispective (retrospective/prospective), multicenter observational study evaluating the real-world efficacy and safety of an obinutuzumab-based strategy in patients with previously untreated advanced FL.
Methods: Patients receiving frontline treatment with obinutuzumab-based immunotherapy, according to the clinical practices of participating Centers, were eligible. Inclusion in the study required at least two completed cycles of induction therapy (retrospective part). The observation period included the obinutuzumab-chemotherapy (CHOP, CVP, or bendamustine) induction phase, maintenance with obinutuzumab every two months, and a one-year follow-up after the last dose. The primary endpoint was the cumulative POD24 rate; secondary endpoints included 2- and 3-year PFS, overall survival (OS), tumor response, necessity for second-line treatments and safety.
Results: A total of 299 patients were enrolled across 46 Italian centers from September 2019 to December 2020. The median age was 62 years (range: 31-83), and 53% were females. ECOG performance status was 0–1 in 96% of the cases. Advanced-stage disease (Ann Arbor stage III–IV) was observed in 94% of cases. The FLIPI score was low in 6%, intermediate in 37%, and high in 57% of patients, respectively. Most of the patients were treated with bendamustine (N=142, 47%) or CHOP (N=139, 46%), while a minority received CVP (N=18, 6%). Among 281 evaluable patients, 25 experienced POD24 (8.9%; 95% CI: 5.8–12.9%), demonstrating a low rate of early progression consistent with GALLIUM trial results. PFS at 2 years was achieved in 256 out of 299 patients (85.6%; 95% CI: 81.1–89.4%), while PFS at 3 years was 76.6% (95% CI: 71.4–81.3%). Overall survival at data cutoff was 81.9% (245/299; 95% CI: 77.1–86.1%). The overall and complete response (CR) rates at end of induction were 96% and 80%, respectively. Sustained CR at 30 months (CR30) was observed in 91% of patients (272/299; 95% CI: 87.1–94%). Thiry-seven of 299 patients (12.4%; 95% CI:8.9%-16.7%) required initiation of a second-line treatment. Obinutuzumab maintenance was started in 88.9% of enrolled patients, however, in 65% of cases, the maintenance plan was modified due to the COVID-19 pandemic (Pinto et al., Br J Haematol 2024). The safety profile of obinutuzumab was consistent with previous reports, with no new safety signals identified. A total of 54 deaths were reported, 31 of which (57%) related to COVID-19. Given the impact of the SARS-CoV-2 pandemic in the study, a sensitivity analysis was conducted excluding COVID-related deaths. Under this analysis, survival outcomes improved, with 2-year PFS increasing to 90.6% (95% CI: 86.8–93.7%), 3-year PFS to 86.3% (95% CI: 81.9–90%), and OS at data cutoff to 92% (95% CI: 88.3–94.8%).
Conclusion: URBAN represents the largest real-world study to date evaluating obinutuzumab-based immunochemotherapy in treatment-naïve patients with advanced FL. The low incidence of POD24 at 8.9% and the durable PFS, along with sustained OS, and a manageable safety profile highlight the overall effectiveness outside of clinical trials. The findings support the use of obinutuzumab-containing regimens as standard frontline practice, confirming their effectiveness in reducing the risk of early progression.
