Papers - UHARA Hisashi

Prognostic role of platelet to lymphocyte and lymphocyte to monocyte ratios in advanced melanoma treated with anti-programmed death-1

Minowa, T. Kato, J. Hida, T. Horimoto, K. Sato, S. Sawada, M. Uhara, H

Eur J Dermatol   1952-4013 (Electronic)  2018  [Refereed]

A case of subepidermal autoimmune bullous disease with autoantibodies against 200 and 290-kDa antigens

Sawada, M. Hida, T. Ujiie, H. Iwata, H. Uhara, H

J Eur Acad Dermatol Venereol   1468-3083 (Electronic)  2018  [Refereed]

Characteristics of adverse drug reactions in a vemurafenib early post-marketing phase vigilance study in Japan

Uhara, H. Kiyohara, Y. Tsuda, A. Takata, M. Yamazaki, N

Clin Transl Oncol   20 ( 2 ) 169 - 175  2018  [Refereed]

Circulating tumour DNA for monitoring treatment response to anti-PD-1 immunotherapy in melanoma patients

Atsuko Ashida, Kaori Sakaizawa, Hisashi Uhara, Ryuhei Okuyama

Acta Dermato-Venereologica ( Medical Journals/Acta D-V )  97 ( 10 ) 1212 - 1218  2017.11  [Refereed]

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Anti-programmed cell death-1 (anti-PD-1) antibody shows high therapeutic efficacy in patients with advanced melanoma. However, assessment of its therapeutic activity can be challenging because of tumour enlargement associated with intratumoural inflammation. Because circulating tumour DNA (ctDNA) correlates with tumour burden, we assessed the value of ctDNA levels as an indicator of tumour changes. Quantification of ctDNA (BRAFmutant or NRASmutant) levels by droplet digital PCR in 5 patients with BRAF or NRAS mutant melanoma during the treatment course showed dynamic changes corresponding to radiological and clinical alterations. In 3 cases in which the anti- PD-1 antibody was effective, ctDNA levels decreased within 2–4 weeks after treatment initiation. In 2 cases in which the anti-PD-1 antibody was ineffective, ctDNA levels did not decrease after treatment initiation. ct- DNA could be a useful biomarker to predict early response to treatment in patients with advanced melanoma treated with anti-PD-1 immunotherapy.

DOI

Phase 2 study to evaluate efficacy and safety of combination therapy with nivolumab (NIVO) and ipilimumab(IPI) in patients with previously untreated melanoma

Y. Kiyohara, T. Takenouchi, H. Uhara, H. Koga, H. Uchi, N. Yamazaki

Annals of Oncology ( Elsevier {BV} )  28   x113 - x114  2017.11

DOI

Circulating tumor DNA for monitoring treatment response to anti-PD-1 immunotherapy in melanoma patients

A. Ashida, K. Sakaizawa, H. Uhara, R. Okuyama

JOURNAL OF INVESTIGATIVE DERMATOLOGY ( ELSEVIER SCIENCE INC )  137 ( 10 ) S291 - S291  2017.10  [Refereed]

【がん分子標的薬の効果と副作用-期待される効果と評価-】 抗体薬 抗PD-1抗体薬、抗CTLA-4抗体薬

宇原久

日本臨床   75 ( 9 ) 1359 - 1364  2017.09  [Refereed]

Nivolumab-related myasthenia gravis with myositis and myocarditis in Japan

Shigeaki Suzuki, Nobuhisa Ishikawa, Fumie Konoeda, Nobuhiko Seki, Satoshi Fukushima, Kikuko Takahashi, Hisashi Uhara, Yoshikazu Hasegawa, Shinichiro Inomata, Yasushi Otani, Kenji Yokota, Takashi Hirose, Ryo Tanaka, Norihiro Suzuki, Makoto Matsui

NEUROLOGY ( LIPPINCOTT WILLIAMS & WILKINS )  89 ( 11 ) 1127 - 1134  2017.09  [Refereed]

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Objective: To report the clinical features of myasthenia gravis (MG) induced by treatment with immune checkpoint inhibitors using 2-year safety databases based on postmarketing surveys in Japan. Methods: We studied 10,277 patients with cancer who had received monotherapy with either nivolumab or ipilimumab between September 2014 and August 2016. As the control group, 105 patients with idiopathic MG were used. Results: There were 12 MG cases (0.12%) among 9,869 patients with cancer who had been treated with nivolumab, but none among 408 patients treated with ipilimumab. These 12 patients included 6 men and 6 women with a mean age of 73.5 6 6.3 years. MG onset occurred in the early phase after nivolumab treatment and rapidly deteriorated. Nivolumab-related MG (nivoMG) included 4 patients with mild involvement and 8 patients with severe involvement. Bulbar symptoms and myasthenic crisis were observed more frequently in nivoMG than idiopathic MG. Ten patients were positive for anti-acetylcholine receptor antibodies. Serum creatine kinase levels were markedly elevated to an average level of 4,799 IU/L. Among the 12 patients with nivoMG, 4 had myositis and 3 had myocarditis, with 1 of these patients having both. Immunosuppressive therapy was effective. Postintervention status showed that pharmacologic remission or minimal manifestations were obtained in 4 patients; however, 2 patients died. Immune-related adverse events triggered by nivolumab impaired the patients' daily living activity. Conclusions: The prompt and correct recognition of MG following treatment with immune checkpoint inhibitors in patients with cancer is important.

DOI

Nail apparatus melanoma thickness is associated with side and age

A. Minagawa, T. Omodaka, H. Koga, Y. Yokokawa, H. Uhara, R. Okuyama

BRITISH JOURNAL OF DERMATOLOGY ( WILEY )  177 ( 3 ) E65 - E66  2017.09  [Refereed]

DOI

【免疫チェックポイント阻害薬 がん薬物療法の新時代】 各腫瘍における免疫チェックポイント阻害薬の現状 悪性黒色腫

宇原久

薬事   59 ( 12 ) 2403 - 2407  2017.09  [Refereed]

抗PD-1抗体をベースとした各種併用療法

宇原久

がん免疫療法   1 ( 2 ) 90 - 91  2017.09  [Refereed]

BRAF/MEK阻害薬が奏効した悪性黒色腫の2例

箕輪 智幸, 加藤 潤史, 江畑 加奈子, 高橋 仁美, 澤田 匡秀, 佐藤 さゆり, 堀本 浩平, 肥田 時征, 宇原 久, 西川 武志

日本皮膚科学会雑誌 ( (公社)日本皮膚科学会 )  127 ( 9 ) 2121 - 2121  2017.08

複数の自己抗体を検出した自己免疫性表皮下水疱症の1例

澤田 匡秀, 肥田 時征, 氏家 英之, 泉 健太郎, 西江 渉, 宇原 久

日本皮膚科学会雑誌 ( (公社)日本皮膚科学会 )  127 ( 9 ) 2117 - 2117  2017.08

強皮症に合併した指尖部潰瘍に対し高圧酸素療法が奏功した1例

安食 さえ子, 菅 裕司, 高橋 宏征, 米田 大介, 山口 華央, 神谷 詩織, 加瀬 貴美, 澄川 靖之, 米田 明弘, 宇原 久

日本皮膚科学会雑誌 ( (公社)日本皮膚科学会 )  127 ( 9 ) 2118 - 2118  2017.08

眼瞼外脂腺癌のダーモスコピー所見と対応する皮膚病理所見の検討

堀本 浩平, 加藤 潤史, 澤田 匡秀, 高橋 仁美, 佐藤 さゆり, 石井 泰江, 神谷 崇文, 肥田 時征, 澄川 靖之, 宇原 久

日本皮膚病理組織学会抄録集 ( 日本皮膚病理組織学会 )  33回   59,36 - 59,36  2017.06

Efficacy and safety of nivolumab in Japanese patients with previously untreated advanced melanoma: A phase II study

Naoya Yamazaki, Yoshio Kiyohara, Hisashi Uhara, Jiro Uehara, Manabu Fujimoto, Tatsuya Takenouchi, Masaki Otsuka, Hiroshi Uchi, Hironobu Ihn, Hironobu Minami

CANCER SCIENCE ( WILEY )  108 ( 6 ) 1223 - 1230  2017.06  [Refereed]

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Treating advanced or recurrent melanoma remains a challenge. Cancer cells can evade the immune system by blocking T-cell activation through overexpression of the inhibitory receptor programmed death 1 (PD-1) ligands. The PD-1 inhibitor nivolumab blocks the inhibitory signal in T cells, thus overcoming the immune resistance of cancer cells. Nivolumab has shown promising anticancer activity in various cancers. We carried out a single-arm, open-label, multicenter, phase II study to investigate the efficacy and safety of nivolumab in previously untreated Japanese patients with advanced melanoma. Twenty-four patients with stage III/IV or recurrent melanoma were enrolled and received i.v. nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was overall response rate evaluated by an independent radiology review committee. The independent radiology review committee-assessed overall response rate was 34.8% (90% confidence interval, 20.8-51.9), and the overall survival rate at 18 months was 56.5% (90% confidence interval, 38.0-71.4). Treatment-related adverse events (AEs) of grade 3 or 4 only occurred in three patients (12.5%). Two patients discontinued nivolumab because of AEs, but all AEs were considered manageable by early diagnosis and appropriate treatment. Subgroup analyses showed that nivolumab was clinically beneficial and tolerable regardless of BRAF genotype, and that patients with treatment-related select AEs and with vitiligo showed tendency for better survival. In conclusion, nivolumab showed favorable efficacy and safety profiles in Japanese patients with advanced or recurrent melanoma, with or without BRAF mutations. (Trial registration no. JapicCTI-142533.)

DOI

Efficacy and safety of nivolumab in Japanese patients with previously untreated advanced melanoma: A phase II study.

Naoya Yamazaki, Yoshio Kiyohara, Hisashi Uhara, Jiro Uehara, Manabu Fujimoto, Tatsuya Takenouchi, Masaki Otsuka, Hiroshi Uchi, Hironobu Ihn, Hironobu Minami

Cancer science   108 ( 6 ) 1223 - 1230  2017.06  [Refereed]  [International journal]

　View Summary

Treating advanced or recurrent melanoma remains a challenge. Cancer cells can evade the immune system by blocking T-cell activation through overexpression of the inhibitory receptor programmed death 1 (PD-1) ligands. The PD-1 inhibitor nivolumab blocks the inhibitory signal in T cells, thus overcoming the immune resistance of cancer cells. Nivolumab has shown promising anticancer activity in various cancers. We carried out a single-arm, open-label, multicenter, phase II study to investigate the efficacy and safety of nivolumab in previously untreated Japanese patients with advanced melanoma. Twenty-four patients with stage III/IV or recurrent melanoma were enrolled and received i.v. nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was overall response rate evaluated by an independent radiology review committee. The independent radiology review committee-assessed overall response rate was 34.8% (90% confidence interval, 20.8-51.9), and the overall survival rate at 18 months was 56.5% (90% confidence interval, 38.0-71.4). Treatment-related adverse events (AEs) of grade 3 or 4 only occurred in three patients (12.5%). Two patients discontinued nivolumab because of AEs, but all AEs were considered manageable by early diagnosis and appropriate treatment. Subgroup analyses showed that nivolumab was clinically beneficial and tolerable regardless of BRAF genotype, and that patients with treatment-related select AEs and with vitiligo showed tendency for better survival. In conclusion, nivolumab showed favorable efficacy and safety profiles in Japanese patients with advanced or recurrent melanoma, with or without BRAF mutations. (Trial registration no. JapicCTI-142533.).

DOI PubMed

脂腺母斑に生じた基底細胞癌のダーモスコピー所見

皆川 茜, 古賀 弘志, 宇原 久, 奥山 隆平

西日本皮膚科 ( 日本皮膚科学会-西部支部 )  79 ( 3 ) 313 - 314  2017.06

Blue gray ovoid nestとarborizing vesselsを示した上眼瞼の紅色結節

皆川 茜, 代田 志保, 古賀 弘志, 宇原 久, 安齋 眞一, 奥山 隆平

日本皮膚病理組織学会抄録集 ( 日本皮膚病理組織学会 )  33回   55,32 - 55,32  2017.06

ベムラフェニブ投与後にPD-L1の発現が増加した悪性黒色腫の1例

加藤 潤史, 高橋 仁美, 澤田 匡秀, 佐藤 さゆり, 堀本 浩平, 神谷 崇文, 肥田 時征, 宇原 久

日本皮膚悪性腫瘍学会学術大会プログラム・抄録集 ( (一社)日本皮膚悪性腫瘍学会 )  33回   147 - 147  2017.05