Real-world efficacy, safety, and predictive factors for response to glofitamab in Chinese patients with relapsed/refractory aggressive B-cell lymphoma: A multicenter study

Abstract Background: Patients with relapsed or refractory (R/R) aggressive B-cell lymphomas, particularly diffuse large B-cell lymphoma (DLBCL), have a poor prognosis. Glofitamab, a CD20xCD3 bispecific antibody, has demonstrated significant efficacy in pivotal clinical trials. However, a pressing need exists for real-world evidence on its effectiveness and safety, especially within heavily pre-treated and heterogeneous patient populations. This study aimed to evaluate the outcomes of glofitamab-based therapy in a real-world cohort of Chinese patients with R/R aggressive B-cell lymphomas and to identify predictive factors for response. Methods: This retrospective, multicenter study enrolled 65 patients with R/R aggressive B-cell lymphoma treated with glofitamab-based regimens. We collected baseline demographic, clinical, and treatment data. The majority of patients received glofitamab as monotherapy (50.8%) or in combination with PD-1 inhibitors (27.7%). Primary efficacy endpoints were the overall response rate (ORR) and complete response (CR) rate. Survival outcomes, including progression-free survival (PFS) and overall survival (OS), were analyzed using the Kaplan-Meier method. Safety was evaluated based on reported adverse events (AEs). Univariate logistic regression analyses were performed to identify predictors for achieving a CR. Results: A total of 65 patients were included in the analysis. The cohort was characterized by high-risk features: 72.3% were older than 60 years, 80.7% had Ann Arbor stage III-IV disease, the median treatment line 4 (range 2-11), and 50.9% had refractory disease. The predominant histology was DLBCL (83.1%), with 67.2% being of the non-germinal center B-cell (non-GCB) subtype. Among 43 efficacy-evaluable patients, the best ORR was 67.4% (95% CI: 51.5%-80.9%), with a CR rate of 46.5%. For the 39 patients in the survival analysis, the median follow-up was 5.88 months (95% CI: 4.24-9.86). The median progression-free survival (PFS) was 6.0 months (95% CI: 4.3-NA) , and the median overall survival (OS) was 13.9 months (95% CI: 12.5-NA). The treatment was well-tolerated, with the most frequent grade ≥3 AEs being anemia (18.2%), neutropenia (15.9%), and leukopenia (13.6%). Cytokine release syndrome (CRS) occurred in 18.2% of patients, and was predominantly low-grade. Severe, grade ≥3 CRS was observed in only 4.5% of patients. Univariate analysis revealed that relapsed disease (vs. refractory, OR=5.06, p=0.020) and the absence of bone marrow involvement (OR=4.44, p=0.039) were associated with a higher likelihood of achieving CR.Conclusion: In this multicenter, real-world study of Chinese patients with R/R aggressive B-cell lymphoma, glofitamab-based therapy demonstrated substantial efficacy, achieving high response rates and promising survival outcomes. At the same time, the safety profile was predictable and manageable, with a low incidence of severe CRS. Our findings suggest that glofitamab is a valuable therapeutic option for this challenging patient population. Disease status (relapsed vs. refractory) and bone marrow involvement were factors significantly associated with complete response in univariate analysis, warranting further validation.