PMID- 33792128 OWN - NLM STAT- MEDLINE DCOM- 20210610 LR - 20210714 IS - 1349-7006 (Electronic) IS - 1347-9032 (Print) IS - 1347-9032 (Linking) VI - 112 IP - 6 DP - 2021 Jun TI - Phase II study of E7777 in Japanese patients with relapsed/refractory peripheral and cutaneous T-cell lymphoma. PG - 2426-2435 LID - 10.1111/cas.14906 [doi] AB - E7777 is a recombinant cytotoxic fusion protein composed of the diphtheria toxin fragments A and B and human interleukin-2. It shares an amino acid sequence with denileukin diftitox, but has improved purity and an increased percentage of active monomer. We undertook a multicenter, single-arm phase II study of E7777 in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL) to evaluate its efficacy, safety, pharmacokinetics, and immunogenicity. A total of 37 patients were enrolled, of which 17 and 19 patients had PTCL and CTCL, respectively, and one patient with another type of lymphoma (extranodal natural killer/T-cell lymphoma, nasal type), diagnosed by the Central Pathological Diagnosis Committee. Among the 36 patients with PTCL and CTCL, objective response rate based on the independent review was 36% (41% and 31%, respectively). The median progression-free survival was 3.1 months (2.1 months in PTCL and 4.2 months in CTCL). The common adverse events (AEs) observed were increased aspartate aminotransferase (AST) / alanine aminotransferase (ALT), hypoalbuminemia, lymphopenia, and pyrexia. Our results indicated that a 9 microg/kg/d dose of E7777 shows efficacy and a manageable safety profile in Japanese patients with relapsed or refractory PTCL and CTCL, with clinical activity observed across the range of CD25 expression. The common AEs were manageable, but increase in ALT / AST, hypoalbuminemia, and capillary leak syndrome should be carefully managed during the treatment. CI - (c) 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. FAU - Kawai, Hidetsugu AU - Kawai H AD - Department of Hematology and Oncology, Tokai University School of Medicine, Isehara, Japan. FAU - Ando, Kiyoshi AU - Ando K AD - Department of Hematology and Oncology, Tokai University School of Medicine, Isehara, Japan. FAU - Maruyama, Dai AU - Maruyama D AUID- ORCID: 0000-0003-0654-6920 AD - Department of Hematology, National Cancer Center Hospital, National Cancer Center Hospital, Tokyo, Japan. FAU - Yamamoto, Kazuhito AU - Yamamoto K AUID- ORCID: 0000-0002-8588-8955 AD - Department of Hematology and Cell Therapy, Aichi Cancer Center, Nagoya, Japan. FAU - Kiyohara, Eiji AU - Kiyohara E AD - Department of Dermatology, Osaka University Hospital, Osaka, Japan. FAU - Terui, Yasuhito AU - Terui Y AD - Department of Hematology Oncology, The Cancer Institute Hospital of JFCR, Tokyo, Japan. FAU - Fukuhara, Noriko AU - Fukuhara N AD - Department of Hematology and Rheumatology, Tohoku University Hospital, Sendai, Japan. FAU - Miyagaki, Tomomitsu AU - Miyagaki T AD - Department of Dermatology, The University of Tokyo Hospital, Tokyo, Japan. FAU - Tokura, Yoshiki AU - Tokura Y AD - Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan. FAU - Sakata-Yanagimoto, Mamiko AU - Sakata-Yanagimoto M AD - Department of Hematology, University of Tsukuba Hospital, Tsukuba, Japan. FAU - Igarashi, Tadahiko AU - Igarashi T AD - Department of Hematology, Gunma Cancer Center, Ota, Japan. FAU - Kuroda, Junya AU - Kuroda J AD - Division of Hematology and Oncology, Kyoto Prefectural University of Medicine, Kyoto, Japan. FAU - Fujita, Jiro AU - Fujita J AD - Department of Dermatology, Osaka University Hospital, Osaka, Japan. FAU - Uchida, Toshiki AU - Uchida T AD - Department of Hematology and Oncology, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan. FAU - Ishikawa, Takayuki AU - Ishikawa T AD - Department of Hematology, Kobe City Medical Center General Hospital, Kobe, Japan. FAU - Yonekura, Kentaro AU - Yonekura K AD - Department of Dermatology, Imamura General Hospital, Kagoshima, Japan. FAU - Kato, Koji AU - Kato K AUID- ORCID: 0000-0002-5815-4585 AD - Department of Hematology and Oncology, Kyushu University Hospital, Fukuoka, Japan. FAU - Nakanishi, Tadashi AU - Nakanishi T AD - Eisai Co., Ltd., Tokyo, Japan. FAU - Nakai, Kenya AU - Nakai K AD - Eisai Co., Ltd., Tokyo, Japan. FAU - Matsunaga, Risa AU - Matsunaga R AD - Eisai Co., Ltd., Tokyo, Japan. FAU - Tobinai, Kensei AU - Tobinai K AD - Department of Hematology, National Cancer Center Hospital, National Cancer Center Hospital, Tokyo, Japan. LA - eng GR - Eisai Co., Ltd/ PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study DEP - 20210503 PL - England TA - Cancer Sci JT - Cancer science JID - 101168776 RN - 0 (Diphtheria Toxin) RN - 0 (E7777 fusion protein) RN - 0 (IL2 protein, human) RN - 0 (Interleukin-2) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Administration, Intravenous MH - Binding Sites MH - Diphtheria Toxin/administration & dosage/adverse effects/chemistry/genetics/pharmacokinetics MH - Drug Administration Schedule MH - Female MH - Humans MH - Interleukin-2/*administration & dosage/adverse effects/chemistry/genetics/pharmacokinetics MH - Japan MH - Lymphoma, T-Cell, Cutaneous/blood/*drug therapy MH - Lymphoma, T-Cell, Peripheral/blood/*drug therapy MH - Male MH - Neoplasm Recurrence, Local/blood/*drug therapy MH - Recombinant Fusion Proteins/*administration & dosage/adverse effects/pharmacokinetics MH - Survival Analysis MH - Treatment Outcome PMC - PMC8177793 OTO - NOTNLM OT - CD25 OT - E7777 OT - cutaneous T-cell lymphoma OT - interleukin-2 OT - peripheral T-cell lymphoma COIS- Ando reports research funding from Eisai. Maruyama reports honoraria and research funding from Eisai. Yamamoto reports consultancy, honoraria, and research funding from Chugai, Ono, Eisai, Mundipharma, Celgene Corporation, and Takeda, honoraria from Sanofi, Kyowa Kirin, Otsuka, Janssen, Sumitomo Dainippon, and Pfizer, honoraria and research funding from Novartis, research funding from Gilead Sciences, SymBio, Bayer, ARIAD, Solasia Pharma, and Incyte, consultancy and honoraria from Bristol-Myers Squibb, MSD, HUYA/IQVIA Services Japan, and Meiji Seika Pharma, and consultancy and research funding from AbbVie and Astra-Zeneca. Kiyohara reports research funding from Eisai. Terui reports research funding from Bristol-Myers Squibb and honoraria from Bristol-Myers Squibb, Celgene, Janssen, Takeda, MSD, Eisai, Ono, and Chugai-Roche Pharmaceuticals Co., Ltd. Fukuhara reports honoraria from Chugai Pharmaceutical Co., Ltd, Kyowa-Hakko Kirin, Mochida, Mundi, Nippon Shinkyaku, Ono Pharmaceutical Co., Ltd, Zenyaku, and Janssen Pharma, honoraria and research funding from Celgene Corporation, Eisai, and Takeda Pharmaceutical Co., Ltd., and research funding from AbbVie, Bayer, Gilead, and Solasia Pharma. Tokura reports honoraria from Eisai Consultancy. Kuroda reports research funding from Eisai. Uchida reports honoraria from Eisai. Nakanishi, Nakai, and Matsunaga report employment by Eisai. Tobinai reports consultancy and honoraria from HUYA Bioscience, Bristol-Myers Squibb, Daiichi Sankyo, Verastem, and Zenyaku Kogyo, consultancy, honoraria, and research funding from Takeda Pharmaceutical, Celgene, Mundi Pharma, and Ono Pharmaceutical, honoraria and research funding from Eisai, Kyowa Kirin, Janssen Pharmaceutical, and Chugai Pharmaceutical, research funding from AbbVie, and honoraria from Yakult, Solasia, and Meiji Seika. EDAT- 2021/04/02 06:00 MHDA- 2021/06/11 06:00 PMCR- 2021/06/01 CRDT- 2021/04/01 06:50 PHST- 2021/03/23 00:00 [revised] PHST- 2021/01/21 00:00 [received] PHST- 2021/03/24 00:00 [accepted] PHST- 2021/04/02 06:00 [pubmed] PHST- 2021/06/11 06:00 [medline] PHST- 2021/04/01 06:50 [entrez] PHST- 2021/06/01 00:00 [pmc-release] AID - CAS14906 [pii] AID - 10.1111/cas.14906 [doi] PST - ppublish SO - Cancer Sci. 2021 Jun;112(6):2426-2435. doi: 10.1111/cas.14906. Epub 2021 May 3.