Transition of the PD-1 occupancy of nivolumab on T cells after discontinuation and response of nivolumab re-challenge

停药后 nivolumab 在 T 细胞上的 PD-1 占有率的变化以及 nivolumab 再次治疗后的反应

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作者:Taku Nose, Yohei Funakoshi, Hirotaka Suto, Yoshiaki Nagatani, Yoshinori Imamura, Masanori Toyoda, Naomi Kiyota, Hironobu Minami

Abstract

Although nivolumab is administered every two or four weeks, high programmed cell death-1 (PD-1) binding of nivolumab on T cells lasting for several months has been reported. A relationship between the PD-1 occupancy rate on T-cells and the efficacy of nivolumab is not yet fully understood. The present study used flow cytometric analyses to determine the time-dependence of PD-1 occupancy in five patients who discontinued nivolumab. The relationship between PD-1 occupancy at relapse and the efficacy of re-challenge was also studied. Occupancies after discontinuation were measured at a total of 32 points. The data indicated that it took 32.4 and 48.9 weeks to decrease occupancy by 50 and 70%, respectively. Subsequently, two patients had recurrence and were re-challenged with nivolumab. At that time, one patient had 70.8% occupancy while the other had 6.6%. Treatment was effective only for the patient with lower occupancy. Overall, the present study suggests that re-challenge with nivolumab may be efficacious in patients with low occupancy at recurrence.

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