Clinical implications of monitoring nivolumab immunokinetics in non–small cell lung cancer patients
Year: 2018
Type: article
Study design: Observational Study
Abstract: BACKGROUND: The PD-1-blocking antibody nivolumab persists in patients several weeks after the last infusion. However, no study has systematically evaluated the maximum duration that the antibody persists on T cells or the association between this duration and residual therapeutic efficacy or potential adverse events. METHODS: To define the duration of binding and residual efficacy of nivolumab after discontinuation, we developed a simplified strategy for T cell monitoring and used it to analyze T cells from peripheral blood from 11 non-small cell lung cancer patients previously treated with nivolumab. To determine the suitability of our method for other applications, we compared transcriptome profiles between nivolumab-bound and nivolumab-unbound CD8 T cells. We also applied T cell monitoring in 2 nivolumab-treated patients who developed progressive lung tumors during long-term follow-up. RESULTS: Prolonged nivolumab binding was detected more than 20 weeks after the last infusion, regardless of the total number of nivolumab infusions (2-15 doses) or type of subsequent treatment, in 9 of the 11 cases in which long-term monitoring was possible. Ki-67 positivity, a proliferation marker, in T cells decreased in patients with progressive disease. Transcriptome profiling identified the signals regulating activation of nivolumab-bound T cells, which may contribute to nivolumab resistance. In 2 patients who restarted nivolumab, T cell proliferation markers exhibited the opposite trend and correlated with clinical response. CONCLUSIONS: Although only a few samples were analyzed, our strategy of monitoring both nivolumab binding and Ki-67 in T cells might help determine residual efficacy under various types of concurrent or subsequent treatment. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry, UMIN000024623. FUNDING: This work was supported by Japan Society for the Promotion of Science KAKENHI (JP17K16045, JP18H05282, and JP15K09220), Japan Agency for Medical Research and Development (JP17cm0106310, JP18cm0106335 and JP18cm059042), and Core Research for Evolutional Science and Technology (JPMJCR16G2).
Source: JCI Insight
Authors: Akio Osa, Takeshi Uenami, Shohei Koyama, Kosuke Fujimoto, Daisuke Okuzaki, Takayuki Takimoto, Haruhiko Hirata, Yukihiro Yano, Soichiro Yokota, Yuhei Kinehara, Yujiro Naito, Tomoyuki Otsuka, Masaki Kanazu, Muneyoshi Kuroyama, Masanari Hamaguchi, Taro Koba, Yu Futami, Mikako Ishijima, Yasuhiko Suga, Yuki Akazawa, Hirotomo Machiyama, Kota Iwahori, Hyota Takamatsu, Izumi Nagatomo, Yoshito Takeda, Hiroshi Kida, Esra A. Akbay, Peter S. Hammerman, Kwok-kin Wong, Glenn Dranoff, Masahide Mori, Takashi Kijima, Atsushi Kumanogoh
Institutions: Immunology Frontier Research Center, The University of Osaka, The University of Osaka, Toneyama National Hospital, National Hospital Organization, Osaka City University, Institute of Medical Science, The University of Tokyo, The University of Tokyo, Research Institute for Microbial Diseases, The University of Osaka, The University of Texas Southwestern Medical Center, NYU Langone Health, NYU Langone’s Laura and Isaac Perlmutter Cancer Center, Institute for Open and Transdisciplinary Research Initiatives
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,100
Awards: MUC1-C Oncoprotein Evades Immune Destruction in Non-small Cell Lung Cancer, Therapeutic strategies for specific subsets of KRAS mutant lung cancers, Investigation on pathological implications of guidance molecules in neuro-immune-metabolism., G5783697281, G6790461652, Regulating the sensitivity of lung cancer to immunotherapy through inhibiting neutrophil activation and promoting T cell infiltration in tumors, Novel disease-specific autoantibodies of difuse interstitial lung diseases
OpenAlex ID: W2895326014