Real-world outcomes of glofitamab-based regimens in relapsed/refractory aggressive B-cell lymphoma

Abstract

Abstract Introduction: Glofitamab, a bispecific antibody targeting CD20 and CD3, is approved for relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) following at least one prior line of therapy, either as monotherapy or in combination with gemcitabine and oxaliplatin (GemOx). However, real-world data on glofitamab-based regimens are lacking. To provide evidence outside of clinical trials, we retrospectively analyzed patients treated with glofitamab-based regimens to evaluate clinical outcomes in r/r aggressive B-cell lymphoma. Methods: This investigator-initiated, retrospective study enrolled consecutive patients with r/r aggressive B-cell lymphoma who received glofitamab-based regimens as salvage at Zhongshan Hospital, Fudan University, between March 2024 and August 2025. Efficacy was assessed by whole-body 18F-FDG PET/CT or contrast-enhanced CT scans. Responses were evaluated using the 2014 Lugano criteria, and adverse events (AEs) were graded per NCI-CTCAE 5.0. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome were graded according to consensus criteria from the American Society for Transplantation and Cellular Therapy. Study endpoints included best complete response (CR) rate, best overall response rate (ORR), safety profiles, progression-free survival (PFS), and overall survival (OS). Subgroup analyses were performed to identify potential predictors of efficacy. Results: A total of 35 consecutive patients were enrolled in this study. The median age was 68 years old (range: 43-94), with 24 patients (68.5%) aged over 60 years old. Three patients (8.5%) had Burkitt lymphoma, and 32 patients (91.4%) had DLBCL. Thirty-four patients (97.1%) were staged Ann-Arbor Ⅲ to Ⅳ, and 24 patients (68.6%) were classified as high-risk by International Prognostic Index score. Other high risk prognostic factors were prevalent in this cohort: 26 patients (74.3%) had elevated lactate dehydrogenase, 34 patients (97.1%) presented with extra-nodal involvement, and 13 patients (37.1%) had bulky diseases. For subtype and biological markers in DLBCL patients, 18 patients were classified as non-germinal center B-cell subtype, 11 patients were diagnosed with double-expressor lymphoma, and 17 patients showed high P53 expression. The median prior lines of treatment exposure were 2 lines (range: 1-6). Specifically, 6 patients (17.1%) had a history of bendamustine exposure, and 4 patients (11.4%) had undergone both autologous stem cell transplantation and chimeric antigen receptor T-cell therapy. As of now, the median number of glofitamab-based regimen cycles administered was 3 (range: 1-12). Among them, the regimens included glofitamab monotherapy (28, 80.0%), glofitamab combination with bruton tyrosine kinase inhibitors (3, 8.6%), GemOx (2, 5.7%), polatuzumab vedotin (1, 2.9%) or dose-reduced ifosfamide, carboplatin and etoposide (1, 2.9%). Twenty-six patients were evaluable for efficacy, and the best CR rate was 26.9% and best ORR was 50.0%. Subgroup analysis showed that similar response rates were observed across various subgroups including age, cell of origin, bulky disease. However, population with normal LDH at baseline tended to benefit more (best CR rate of normal vs elevated LDH: 57.1% vs. 15.8%) from glofitamab-based regimens. Compared to those who did not achieve CR, patients in best CR subgroup had a significant higher CD4-positive T-cell count (CR vs non-CR: 418 [138] vs 251 [144], mean [SD], p=0.03). The most common AEs were anemia (85.7%), leukocytopenia (54.3%), neutropenia (54.3%), and CRS (28.6%), most of which were grade 1-2. With a median follow-up of 5.5 months (95% CI: 1.4-not applicable), the median PFS was 2.6 months (95% CI: 2.17-not applicable), and the median OS was not reached. Conclusions: Our findings characterize disease features of heavily treated r/r aggressive B-cell lymphoma and real-world outcomes with glofitamab-based salvage. Even in the subgroups with adverse prognosis factors, glofitamab-based regimens still demonstrated efficacy and manageable toxicities.