Abstract Background: Glofitamab, a CD20×CD3 bispecific antibody, has shown remarkable efficacy in relapsed or refractory (R/R) aggressive B-cell lymphomas in clinical trials. While the STARGLO study established the therapeutic benefit of glofitamab combined with GEMOX, real-world evidence remains limited, particularly regarding its efficacy with other salvage regimens. This prospective observational study evaluated glofitamab-based combination therapy in Chinese patients with R/R aggressive B-cell lymphomas who received ≥2 prior lines of therapy. The study was approved by the institutional review board (20240430041615581) and registered at ClinicalTrials.gov (NCT06497452). Methods: Patients aged ≥18 years with R/R aggressive B-cell lymphomas received glofitamab plus salvage therapy (GEMOX, DHAP, EPOCH, or other regimens). Pretreatment included obinutuzumab 1000mg (Cycle 1 Day 1), followed by glofitamab step-up dosing (2.5mg C1D8, 10mg C1D15, 30mg from C2D1). Salvage therapy was administered at standard doses. Safety was assessed per cycle, and efficacy was evaluated via PET-CT at screening and every two cycles. Results: As of July 20, 2025, a total of 66 patients were enrolled in this study.Of the 66 patients (28 female and 38 male) , the median age was 54 years (range: 18–87). All patients had IPI scores ≥ 3 and had advanced disease (Ann Arbor stage III/IV: 66/66). Histologic subtypes included DLBCL (64/66, with transformations from follicular lymphoma, marginal zone lymphoma, and Richter's syndrome),while other pathologic types included 1 Burkitt's lymphoma and 1 high-grade B-cell lymphoma. Of the 64 cases of DLBCL, 40 originated from germinal centers and 22 from non-germinal centers. Adverse prognostic factors mainly include positive expression of MYC and BCL2 (double expression;21/64) and bulky disease (≥7cm;13/66) . 52 patients experienced 3 or more lines of treatment. 10 patients underwent autologous stem-cell transplantation (ASCT), and another 8 had received chimeric antigen receptor (CAR) T-cell therapies previously. The overall response rate (ORR) and complete response (CR) (as best response) rate in 44 efficacy-evaluable DLBCL patients were 84.1% (37/44) and 43.2% (19/44), respectively. Univariate analysis revealed that non-GCB subtype was significantly associated with CR. While Age, gender, stage, number of treatment lines received, whether previous transplantation or CART was not significantly associated with CR. Median overall survival and median progression-free survival were not reached.The median follow-up period was 9.2 months. The 1-year PFS rate was 60.75%, and the 1-year OS rate was 60.85%.Overall, our data show that the ORR and 1-year PFS were superior to the results observed in the STARGLO study. Among the 66 safety-evaluable patients, 36 patients (67.9%) experienced cytokine release syndrome (CRS). Most of the CRS events were low grade (Grade 1: 68.2% ). Immune effector cell-associated neurotoxicity syndrome occurred in 4 patients and immune-related myocardial injury in 1 patient. The most common Grade 3/4 adverse event (AE) was neutropenia (31/66; 46.9%), which was mainly due to the combined chemotherapeutic drugs. The incidence of infection was 36.7%, and the rate of grade 3+ infections was 17.2%. No Grade 5 AEs were reported. Conclusions: This real-world study demonstrates favorable efficacy and manageable safety of glofitamab-based salvage therapy in R/R aggressive B-cell lymphomas. Combination therapy significantly improved outcomes, with no regimen-dependent differences observed. CRS and infections require vigilant monitoring, but the regimen offers a promising therapeutic option for this refractory population.
You et al. (Mon,) studied this question.