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. 2022 May;16(5):104.
doi: 10.3892/mco.2022.2537. Epub 2022 Apr 12.

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

Taku Nose  1 , Yohei Funakoshi  1 , Hirotaka Suto  1 , Yoshiaki Nagatani  1 , Yoshinori Imamura  1 , Masanori Toyoda  1 , Naomi Kiyota  1   2 , Hironobu Minami  1   2
Affiliations

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

Taku Nose et al. Mol Clin Oncol. 2022 May.

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.

Keywords: nivolumab re-challenge; occupancy; programmed cell death-1.

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Conflict of interest statement

Hironobu Minami has received research grants and honoraria from Bristol-Myers Squibb and Chugai Pharmaceutical. Naomi Kiyota has received research grants from Bristol-Myers Squibb. The other authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
PD-1 binding vs. time. Binding of nivolumab to T cells was determined at 32 different time-points after discontinuation of treatment. The broken line was derived by linear regression of the data.
Figure 2
Figure 2
Temporal changes in nivolumab binding to T cell PD-1. The x-axis indicates weeks after the final dose of nivolumab. After discontinuation of treatment, binding was determined for each patient periodically. Arrows indicate when disease recurrence was observed in patients 4 and 5. The star indicates the occupancy rate after re-challenged with nivolumab in Patient 5.
Figure 3
Figure 3
Axial computed tomography of patients 4 and 5 at the time of recurrence and after resumption of nivolumab treatment. Arrows indicate each tumor.
See this image and copyright information in PMC

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