Oral histone deacetylase inhibitor tucidinostat (HBI‐8000) in patients with relapsed or refractory adult T‐cell leukemia/lymphoma: Phase IIb results

• Published in: Cancer science Vol. 113; no. 8; pp. 2778 - 2787
• Main Authors: Utsunomiya, Atae, Izutsu, Koji, Jo, Tatsuro, Yoshida, Shinichiro, Tsukasaki, Kunihiro, Ando, Kiyoshi, Choi, Ilseung, Imaizumi, Yoshitaka, Kato, Koji, Kurosawa, Mitsutoshi, Kusumoto, Shigeru, Miyagi, Takashi, Ohtsuka, Eiichi, Sasaki, Osamu, Shibayama, Hirohiko, Shimoda, Kazuya, Takamatsu, Yasushi, Takano, Kuniko, Yonekura, Kentaro, Makita, Shinichi, Taguchi, Jun, Gillings, Mireille, Onogi, Hiroshi, Tobinai, Kensei
• Format: Journal Article
• Language: English
• Published: Tokyo John Wiley & Sons, Inc 01.08.2022; John Wiley and Sons Inc
• Subjects: Apoptosis; ATLL; Chemotherapy; Drug dosages; Gene expression; HBI‐8000; HDAC inhibitor; Hemoglobin; Histone deacetylase; Infections; Leukemia; Leukocytes (neutrophilic); Lymphoma; Medical prognosis; Original; ORIGINAL ARTICLES; ORR; Palliative care; Patients; Response rates; Transplants & implants; tucidinostat; United States > US; China; Japan
• ISSN: 1347-9032; 1349-7006; 1349-7006
• DOI: 10.1111/cas.15431

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. Tucidinostat is an oral novel benzamide HDACi of HDAC isoenzymes 1, 2, 3 and 10 selectively. 23 patients with relapsed/refractory ATLL were treated with tucidinostat 40mg orally twice a week. Out of 23 patients, 7 showed objective responses including 1 CR, and ORR was 30.4%.