@article{08c9d47a25164062981e843c0cb033fb,
title = "Final results of a phase II study of nivolumab in Japanese patients with relapsed or refractory classical Hodgkin lymphoma",
abstract = "Background: Many patients with classical Hodgkin lymphoma show increased programmed death-1 ligand expression in Reed-Sternberg cells. We report the final results of a phase II study of nivolumab, an anti-programmed death-1 monoclonal antibody, in Japanese patients with relapsed or refractory classical Hodgkin lymphoma. Methods: Japanese patients with previously treated classical Hodgkin lymphoma (aged ≥ 20 years) were administered nivolumab (3 mg/kg on Day 1 of 14-day cycles) until progressive disease, an unacceptable adverse event, or another clinically relevant reason. Treatment could continue beyond progressive disease at the investigator's discretion in selected patients. Results: Seventeen patients (median age: 63.0 years) were enrolled. The median follow-up was 38.8 months. One patient with non-Hodgkin lymphoma was excluded from efficacy analyses. The centrally assessed overall response rate in 16 classical Hodgkin lymphoma patients was 87.5% (95% confidence interval = 61.7-98.4%) and the disease control rate was 93.8% (95% confidence interval = 69.8-99.8%). The median (95% confidence interval) duration of response and progression-free survival were 8.5 (2.4-12.6) and 11.7 (1.8-42.3) months, respectively. The 3-year overall survival rate was 80.4% (95% confidence interval = 50.6-93.2%). Nivolumab was continued beyond progressive disease in seven patients; six were alive at the data cut-off. Adverse drug reactions occurred in all 17 patients with grades 3-4 adverse drug reactions in eight patients and no grade 5 adverse drug reactions. Pulmonary toxicities occurred in five patients; four of these occurred ≥17 months after starting nivolumab. Conclusion: Nivolumab is effective and tolerable in Japanese relapsed or refractory classical Hodgkin lymphoma patients. Continued monitoring may be necessary to detect late-onset pulmonary toxicities.",
keywords = "Disease progression, Hodgkin lymphoma, Interstitial lung disease, Nivolumab, Survival",
author = "Dai Maruyama and Yasuhito Terui and Kazuhito Yamamoto and Noriko Fukuhara and Ilseung Choi and Junya Kuroda and Kiyoshi Ando and Akira Hattori and Kensei Tobinai",
note = "Funding Information: The authors thank all of the patients and relatives who participated in this study, as well as the investigators and staff at all of the institutions involved in conducting this study. The authors also thank Koichi Ohshima (Kurume University Hospital, Fukuoka) and Jun-Ichi Tamaru (Saitama Medical Center, Saitama) for their support in the Central Pathological Review Committee and Kazuo Tamura (Fukuoka University Hospital, Fukuoka), Kunihiro Tsukasaki (National Cancer Center Hospital East, Chiba), Kenichi Ishizawa (Yamagata University Faculty of Medicine, Yamagata), Terufumi Kato (Kanagawa Cancer Center, Yokohama) and Masashi Takahashi (Yujinkai Yujin-Yamazaki Hospital, Shiga) for reviewing the clinical data as members of the Efficacy and Safety Evaluation Committee. The authors thank Nicholas D. Smith (EMC K.K.) for medical writing support, which was funded by Ono Pharmaceutical Co., Ltd. Funding Information: This study was funded by Ono Pharmaceutical Co., Ltd. and Bristol-Myers Squibb K.K. Funding Information: D. Maruyama has received research grants and personal fees from Ono Pharmaceutical, Celgene, Takeda, Janssen Pharmaceutical, Chugai Pharmaceutical and Bristol-Myers Squibb; research grants from Merck, Amgen Astellas BioPharma, Astellas Pharma, Sanofi, Novartis and Otsuka Pharmaceutical; Funding Information: personal fees from Eisai, Kyowa Kirin, Zenyaku Kogyo, Synmosa Biopharma and Nippon Shinyaku. Y. Terui has received research grants and personal fees from Bristol-Myers Squibb; personal fees from Ono Pharmaceutical, Celgene, Chugai Pharmaceutical, Janssen Pharmaceutical and Novartis. K. Yamamoto has received research grants and personal fees from Ono Pharmaceutical, Abb-Vie, AstraZeneca, Celgene, Chugai Pharmaceutical, Eisai, MSD, Mundipharma, Nippon Shinyaku, Novartis, Otsuka Pharmaceutical, Takeda, Zenyaku Kogyo; research grants from ARIAD Pharmaceuticals, Bayer, Gilead Sciences, Incyte, Solasia Pharma and SymBio Pharmaceuticals; personal fees from Bristol-Myers Squibb, Daiichi Sankyo, HUYA Bioscience International, IQVIA, Janssen Pharmaceutical, Kyowa Kirin, Meiji Seika Pharma, Mochida Pharmaceutical, Pfizer, Sanofi, Stemline Therapeutics and Sumitomo Dainippon Pharma. N. Fukuhara has received research grants and personal fees from Chugai Pharmaceutical, Eisai, Kyowa Kirin, Janssen Pharmaceutical, Ono Pharmaceutical, Takeda, Celgene and AbbVie; research grants from Bayer, Solasia Pharma and Gilead Sciences; personal fees from Mochida Pharmaceutical, Mundipharma, Nippon Shinyaku, Zenyaku Kogyo, Stemline Therapeutics, HUYA Bioscience International, IQVIA and Novartis. I. Choi has nothing to disclose. J. Kuroda has received research grants and personal fees from Astellas Pharma, Kyowa Kirin, Chugai Pharmaceutical, Japan Blood Products Organization, Daiichi Sankyo, Mochida Pharmaceutical, Celgene, Ono Pharmaceutical, Sanofi, Eisai, Sumitomo Dainippon Pharma, Asahi Kasei Pharma, Otsuka Pharmaceutical, MSD, Takeda, Fujimoto and Nippon Shinyaku; research grants from Pfizer, Taiho Pharmaceutical, Shionogi, Nihon Pharmaceutical and Sysmex; personal fees from Janssen Pharmaceutical and AbbVie. K. Ando has received research grants from Ono Pharmaceutical. A. Hattori is an employee of Ono Pharmaceutical. K. Tobinai has received research grants and personal fees from Ono Pharmaceutical, Eisai, Takeda, Mundipharma, Kyowa Kirin, Celgene and Chugai Pharmaceutical; research grants from Janssen Pharmaceutical and AbbVie; personal fees from Zenyaku Kogyo, HUYA Bioscience International, Yakult Honsha, Daiichi Sankyo, Bristol-Myers Squibb, Meiji Seika Pharma, Solasia Pharma and Verastem Oncology. The study sponsors were involved in study design, writing of the report, and in the decision to submit the article for publication. The study drug was provided by Ono Pharmaceutical. Ono Pharmaceutical collected and analyzed the data, and contributed to the interpretation of the study. All authors had full access to all of the data in the study and had final responsibility for the decision to submit for publication. Publisher Copyright: {\textcopyright} The Author(s) 2020. Published by Oxford University Press.",
year = "2020",
doi = "10.1093/JJCO/HYAA117",
language = "English",
volume = "50",
pages = "1265--1273",
journal = "Japanese Journal of Clinical Oncology",
issn = "0368-2811",
publisher = "Oxford University Press",
number = "11",
}