Katlinskaya Yuliya, Panwar Bharat, Zeng Yi, Gordon Paul, Rasmussen Erik, Naegele Virginie, Klinger Matthias, Zugmaier Gerhard
Amgen Inc., Thousand Oaks, CA, United States.
Amgen Research (Munich) GmbH, Munich, Germany.
Oncologist. 2025 Jun 4;30(6). doi: 10.1093/oncolo/oyaf137.
Blinatumomab, a bispecific T-cell engager, requires the activity of CD3+ T-cells for tumor lysis. This pooled analysis aimed to re-examine baseline T regulatory cells (Tregs) as a biomarker of blinatumomab efficacy across multiple clinical trials and provide insights into peripheral T-cell dynamics during blinatumomab therapy in hematological malignancies.
Tregs and peripheral T-cells were enumerated by fluorescence-activated cell sorting and were statistically evaluated using the Wilcoxon rank-sum test and linear mixed effect modeling, respectively.
Comparable baseline percentages of Tregs were observed in responders and non-responders of blinatumomab treatment (N = 325) in adults with leukemia or lymphoma. Peripheral T-cell count recovery occurred early during blinatumomab dosing, and before blinatumomab-free interval in patients (N = 233) from 4 clinical trials.
The pooled analysis revealed that baseline Treg levels do not serve as a predictive marker for blinatumomab response and that there is rapid peripheral T-cell recovery following blinatumomab dosing. These results suggest that patients with varying levels of Tregs can benefit from blinatumomab treatment and that blinatumomab-free intervals of 7 days may suffice in blinatumomab treatment regimens.
双特异性T细胞衔接器blinatumomab需要CD3+ T细胞的活性来实现肿瘤溶解。这项汇总分析旨在重新审视基线调节性T细胞（Tregs）作为blinatumomab在多个临床试验中疗效的生物标志物，并深入了解血液系统恶性肿瘤患者接受blinatumomab治疗期间外周T细胞动力学。
通过荧光激活细胞分选对Tregs和外周T细胞进行计数，并分别使用Wilcoxon秩和检验和线性混合效应模型进行统计学评估。
在患有白血病或淋巴瘤的成人blinatumomab治疗应答者和非应答者（N = 325）中观察到Tregs的基线百分比相当。在4项临床试验的患者（N = 233）中，外周T细胞计数在blinatumomab给药早期恢复，且在无blinatumomab间隔期之前恢复。
汇总分析表明，基线Treg水平不能作为blinatumomab反应的预测标志物，且blinatumomab给药后外周T细胞可快速恢复。这些结果表明，不同Treg水平的患者均可从blinatumomab治疗中获益，且blinatumomab治疗方案中7天的无blinatumomab间隔期可能足够。
