Journal Article

TP53 mutations and baseline lymphocytes indicate response to glofitamab in relapsed or refractory diffuse large B-cell lymphoma

Zhou, Daobin, Zhao, Danqing, Zhang, Wei, Ruan, Jing, Zhang, Yan, Wei, Chong, Li, Jian

2026

Overview

Although CAR-T cell therapy has emerged as a promising therapeutic option for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), long manufacturing time, high cost and toxicities limit its clinical use. T-cell engagers (TCEs) including glofitamab may address these unmet needs, but real-world data remain scarce. This real-world study (NCT06481826) enrolled 30 Chinese patients. The median prior treatment lines were 2 (2–5) and 90% had no prior CAR-T therapy. After a median follow-up of 15 months, the overall response rate (ORR) was 66.7%. The 1-year progression-free survival (PFS) was 62.5% with a median PFS of 15 months. The 1-year overall survival (OS) was 70%. Univariate analysis identified more than 1 extranodal involvement site, TP53 mutation and low baseline lymphocytes as poor prognostic factors. Safety profile was manageable. 43.3% patients developed cytokine release syndrome (CRS, mostly grade 1–3) and 3.3% had grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS). The hematologic toxicity was mostly mild. COVID-19 infection occurred in 20% of patients. This study demonstrates that glofitamab is effective and well-tolerated in Chinese R/R DLBCL patients. Earlier lines of glofitamab may be more beneficial, while expanded cohorts are warranted to explore its efficacy among patients with multiple extranodal lesions, TP53 mutations and low baseline lymphocytes. Highlights Glofitamab is effective and well-tolerated in Chinese R/R DLBCL patients. Multiple extranodal lesions, TP53 mutations and low baseline lymphocytes are associated with poor response to glofitamab. Earlier lines of glofitamab may be more beneficial.

• Publisher: Springer Berlin Heidelberg,Springer Nature B.V,Springer
• Subject: Adult / Aged / Diffuse large B-cell lymphoma / Female / Genetic testing / Glofitamab / Hematology / Humans / Immunotherapy, Adoptive / Lymphocytes / Lymphoma / Lymphoma, Large B-Cell, Diffuse - drug therapy / Lymphoma, Large B-Cell, Diffuse - genetics / Lymphoma, Large B-Cell, Diffuse - mortality / Lymphoma, Large B-Cell, Diffuse - therapy / Male / Medical prognosis / Medicine / Medicine & Public Health / Middle Aged / Mutation / Oncology / Patients / Stem cell transplantation / Survival analysis / Tomography / TP53 mutation / Tumor Suppressor Protein p53 - genetics