Early CD3+ T-Cell Dynamics in a Case Series of Patients with Relapsed/Refractory Aggressive B-Cell Lymphoma Treated with Glofitamab:Exploratory Observations

Background: Glofitamab, a novel CD20xCD3 bispecific T-cell engager, has demonstrated therapeutic potential in patients with relapsed or refractory (R/R) aggressive B-cell lymphomas. However, reliable early response biomarkers for treatment of glofitamab remain unidentified. This exploratory case series aimed to describe the clinical outcomes of six patients with R/R B-cell lymphoma treated with glofitamab-based therapies and to investigate the potential association of the T1/T0 ratio as an early indicator of treatment response. The T1/T0 ratio, which quantifies the fold change in CD3⁺ T cell percentage following treatment compared to baseline measurements, was assessed as a potential biomarker for exploratory assessment of therapeutic response. Methods: A cohort of six patients with R/R B-cell lymphoma received glofitamab-based treatment regimens. Treatment responses were rigorously assessed using 18F-FDG PET-CT imaging according to Deauville criteria (Lugano classification). Longitudinal immune profiling was conducted using multiparametric flow cytometry to monitor T-cell subset dynamics. The baseline (T0) measurement was obtained on the day before glofitamab administration. The post-treatment (T1) measurement was collected within 7 days after the first cycle of glofitamab (before cycle 2). The T1/T0 ratios were subsequently observed and correlated with clinical outcomes. Results: The clinical response to glofitamab varied among patients. Three patients achieved complete response (CR), one maintained stable disease (SD), and two exhibited progressive disease (PD). Notably, patients who achieved a CR demonstrated a higher median T1/T0 ratio (median: 1.16) compared to those with SD or PD (median: 0.91). Statistical testing was not performed due to limited sample size. Treatment-related cytokine release syndrome was observed in three patients, all of whom were successfully managed with tocilizumab. Conclusion:In this limited cohort, glofitamab demonstrated the potential to elicit responses in heavily pretreated patients with R/R aggressive B-cell lymphomas. Furthermore, the T1/T0 ratio, reflecting the post-treatment expansion of CD3+ T-cells, was observed to potentially serve as an early indicator for clinical response. These preliminary findings suggest an association between T-cell dynamics and clinical response to glofitamab. Further validation in larger prospective studies is warranted to confirm these findings.