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

• Published in: Molecular and clinical oncology Vol. 16; no. 5; p. 104
• Main Authors: Nose, Taku, Funakoshi, Yohei, Suto, Hirotaka, Nagatani, Yoshiaki, Imamura, Yoshinori, Toyoda, Masanori, Kiyota, Naomi, Minami, Hironobu
• Format: Journal Article
• Language: English
• Published: England Spandidos Publications 01.05.2022; Spandidos Publications UK Ltd; D.A. Spandidos
• Subjects: Analysis; Antibodies; Apoptosis; Binding sites; Cancer therapies; Cell death; Clinical trials; Flow cytometry; Immunotherapy; Lung cancer; Lymphocytes; Metastasis; Monoclonal antibodies; Oncology; Patients; T cells; Targeted cancer therapy; Trends; United States > US; occupancy; nivolumab re-challenge; programmed cell death-1
• ISSN: 2049-9450; 2049-9469
• DOI: 10.3892/mco.2022.2537

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.