PMID- 35579212 OWN - NLM STAT- MEDLINE DCOM- 20220809 LR - 20220810 IS - 1349-7006 (Electronic) IS - 1347-9032 (Print) IS - 1347-9032 (Linking) VI - 113 IP - 8 DP - 2022 Aug TI - Oral histone deacetylase inhibitor tucidinostat (HBI-8000) in patients with relapsed or refractory adult T-cell leukemia/lymphoma: Phase IIb results. PG - 2778-2787 LID - 10.1111/cas.15431 [doi] AB - This multicenter, prospective phase IIb trial evaluating the efficacy and safety of tucidinostat (HBI-8000) in patients with relapsed or refractory (R/R) adult T-cell leukemia/lymphoma (ATLL) was undertaken in Japan. Eligible patients had R/R ATLL and had failed standard of care treatment with chemotherapy and with mogamulizumab. Twenty-three patients received tucidinostat 40 mg orally twice per week and were included in efficacy and safety analyses. The primary end-point was objective response rate (ORR) assessed by an independent committee. The ORR was 30.4% (95% confidence interval [CI], 13.2, 52.9]. Median progression-free survival was 1.7 months (95% CI, 0.8, 7.4), median duration of response was 9.2 months (95% CI, 2.6, not reached), and median overall survival was 7.9 months (95% CI, 2.3, 18.0). All patients experienced adverse events (AEs), which were predominantly hematologic and gastrointestinal. Incidence of grade 3 or higher AEs was 78.3%; most were laboratory abnormalities (decreases in platelets, neutrophils, white blood cells, and hemoglobin). Tucidinostat was well tolerated with AEs that could be mostly managed with supportive care and dose modifications. Tucidinostat is a meaningful treatment option for R/R ATLL patients; further investigation is warranted. CI - (c) 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. FAU - Utsunomiya, Atae AU - Utsunomiya A AUID- ORCID: 0000-0002-8843-406X AD - Department of Hematology, Imamura General Hospital, Kagoshima, Japan. FAU - Izutsu, Koji AU - Izutsu K AUID- ORCID: 0000-0001-9129-8057 AD - Department of Hematology, National Cancer Center Hospital, Tokyo, Japan. FAU - Jo, Tatsuro AU - Jo T AD - Department of Hematology, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan. FAU - Yoshida, Shinichiro AU - Yoshida S AD - Department of Hematology, National Hospital Organization Nagasaki Medical Center, Japan. FAU - Tsukasaki, Kunihiro AU - Tsukasaki K AD - Department of Hematology, International Medical Center, Saitama Medical University, Saitama, Japan. FAU - Ando, Kiyoshi AU - Ando K AD - Department of Hematology/Oncology, Tokai University Hospital, Kanagawa, Japan. FAU - Choi, Ilseung AU - Choi I AD - Department of Hematology, NHO Kyushu Cancer Center, Fukuoka, Japan. FAU - Imaizumi, Yoshitaka AU - Imaizumi Y AUID- ORCID: 0000-0002-2954-5691 AD - Department of Hematology, Nagasaki University Hospital, Nagasaki, Japan. FAU - Kato, Koji AU - Kato K AUID- ORCID: 0000-0002-5815-4585 AD - Department of Hematology, Oncology and Cardiovascular Medicine, Kyushu University Hospital, Fukuoka, Japan. FAU - Kurosawa, Mitsutoshi AU - Kurosawa M AD - Department of Hematology, Hokkaido Cancer Center, Sapporo, Japan. FAU - Kusumoto, Shigeru AU - Kusumoto S AUID- ORCID: 0000-0001-6546-1279 AD - Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan. FAU - Miyagi, Takashi AU - Miyagi T AD - Department of Hematology, Heartlife Hospital, Okinawa, Japan. FAU - Ohtsuka, Eiichi AU - Ohtsuka E AD - Department of Hematology, Oita Prefectural Hospital, Oita, Japan. FAU - Sasaki, Osamu AU - Sasaki O AD - Division of Hematology, Miyagi Cancer Center, Miyagi, Japan. FAU - Shibayama, Hirohiko AU - Shibayama H AD - Department of Hematology and Oncology, Osaka University Hospital, Suita, Japan. FAU - Shimoda, Kazuya AU - Shimoda K AD - Division of Hematology, Diabetes and Endocrinology, Department of Internal Medicine, University of Miyazaki, Miyazaki, Japan. FAU - Takamatsu, Yasushi AU - Takamatsu Y AD - Department of Medical Oncology, Hematology and Infectious Diseases, Fukuoka University Hospital, Fukuoka, Japan. FAU - Takano, Kuniko AU - Takano K AD - Department of Medical Oncology and Hematology, Faculty of Medicine, Oita University Hospital, Oita University, Oita, Japan. FAU - Yonekura, Kentaro AU - Yonekura K AUID- ORCID: 0000-0002-9030-247X AD - Department of Dermatology, Imamura General Hospital, Kagoshima, Japan. FAU - Makita, Shinichi AU - Makita S AUID- ORCID: 0000-0001-6609-8088 AD - Department of Hematology, National Cancer Center Hospital, Tokyo, Japan. FAU - Taguchi, Jun AU - Taguchi J AD - Department of Hematology, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan. FAU - Gillings, Mireille AU - Gillings M AD - HUYABIO International, CEO, Corporate Office, San Diego, California, USA. FAU - Onogi, Hiroshi AU - Onogi H AD - Research & Development, Huya Japan GK, Tokyo, Japan. FAU - Tobinai, Kensei AU - Tobinai K AD - Department of Hematology, National Cancer Center Hospital, Tokyo, Japan. LA - eng GR - The study was funded by HUYABIO International, LLC./ PT - Journal Article PT - Multicenter Study DEP - 20220607 PL - England TA - Cancer Sci JT - Cancer science JID - 101168776 RN - 0 (Benzamides) RN - 0 (HBI-8000) RN - 0 (Histone Deacetylase Inhibitors) RN - 0 (Pyridines) SB - IM MH - Adult MH - Benzamides MH - Histone Deacetylase Inhibitors/adverse effects MH - Humans MH - *Leukemia-Lymphoma, Adult T-Cell/drug therapy MH - *Lymphoma, Follicular/drug therapy MH - Prospective Studies MH - Pyridines MH - Recurrence MH - Treatment Outcome PMC - PMC9357668 OTO - NOTNLM OT - ATLL OT - HBI-8000 OT - HDAC inhibitor OT - ORR OT - tucidinostat EDAT- 2022/05/18 06:00 MHDA- 2022/08/10 06:00 PMCR- 2022/08/01 CRDT- 2022/05/17 06:33 PHST- 2022/05/09 00:00 [revised] PHST- 2022/02/21 00:00 [received] PHST- 2022/05/12 00:00 [accepted] PHST- 2022/05/18 06:00 [pubmed] PHST- 2022/08/10 06:00 [medline] PHST- 2022/05/17 06:33 [entrez] PHST- 2022/08/01 00:00 [pmc-release] AID - CAS15431 [pii] AID - 10.1111/cas.15431 [doi] PST - ppublish SO - Cancer Sci. 2022 Aug;113(8):2778-2787. doi: 10.1111/cas.15431. Epub 2022 Jun 7.