An open-label, single-arm phase 2 trial of valemetostat for relapsed or refractory adult T-cell leukemia/lymphoma
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- Koji Izutsu
- 1Department of Hematology, National Cancer Center Hospital, Tokyo, Japan
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- Shinichi Makita
- 1Department of Hematology, National Cancer Center Hospital, Tokyo, Japan
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- Kisato Nosaka
- 2Department of Hematology, Rheumatology and Infectious Diseases, Kumamoto University Hospital, Kumamoto, Japan
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- Makoto Yoshimitsu
- 3Department of Hematology and Rheumatology, Kagoshima University Hospital, Kagoshima, Japan
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- Atae Utsunomiya
- 4Department of Hematology, Imamura General Hospital, Kagoshima, Japan
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- Shigeru Kusumoto
- 5Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
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- Satoko Morishima
- 6Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology, Second Department of Internal Medicine, Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan
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- Kunihiro Tsukasaki
- 7Department of Hematology, International Medical Center, Saitama Medical University, Saitama, Japan
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- Toyotaka Kawamata
- 8Department of Hematology/Oncology, Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
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- Takaaki Ono
- 9Department of Transfusion and Cell Therapy, Hamamatsu University Hospital, Shizuoka, Japan
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- Shinya Rai
- 10Department of Hematology and Rheumatology, Faculty of Medicine, Kindai University, Osaka, Japan
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- Hiroo Katsuya
- 11Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan
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- Jun Ishikawa
- 12Department of Hematology, Osaka International Cancer Institute, Osaka, Japan
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- Hironori Yamada
- 13Daiichi Sankyo Co, Ltd, Tokyo, Japan
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- Kazunobu Kato
- 14Daiichi Sankyo, Inc, Basking Ridge, NJ
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- Masaya Tachibana
- 13Daiichi Sankyo Co, Ltd, Tokyo, Japan
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- Yasuyuki Kakurai
- 13Daiichi Sankyo Co, Ltd, Tokyo, Japan
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- Nobuaki Adachi
- 13Daiichi Sankyo Co, Ltd, Tokyo, Japan
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- Kensei Tobinai
- 1Department of Hematology, National Cancer Center Hospital, Tokyo, Japan
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- Kentaro Yonekura
- 15Department of Dermatology, Imamura General Hospital, Kagoshima, Japan
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- Kenji Ishitsuka
- 3Department of Hematology and Rheumatology, Kagoshima University Hospital, Kagoshima, Japan
抄録
<jats:title>Abstract</jats:title> <jats:p>Adult T-cell leukemia/lymphoma (ATL) is an aggressive non-Hodgkin lymphoma with poor prognosis and few treatment options for patients with relapsed, recurrent, or refractory disease. We evaluated the efficacy and safety of valemetostat, a potent enhancer of zeste homolog 2 (EZH2) and EZH1 inhibitor, in treating relapsed or refractory (R/R) ATL. This multicenter phase 2 trial enrolled patients with R/R aggressive ATL (acute, lymphoma, unfavorable chronic type). Patients received valemetostat 200 mg/day orally until progressive disease or unacceptable toxicity. The primary end point was overall response rate (ORR) centrally assessed by an independent efficacy assessment committee (IEAC). Secondary end points included best response in disease compartments, duration of response (DOR), pharmacokinetics, and safety. Twenty-five patients (median age, 69.0 years) with a median of 3 prior lines of therapy were enrolled; 24 had prior mogamulizumab treatment. The primary end point was met with a centrally reviewed ORR of 48.0% (90% confidence interval [CI], 30.5-65.9), including 5 complete and 7 partial remissions. Patients pretreated with mogamulizumab had an ORR of 45.8% (4 complete and 7 partial remissions). IEAC-assessed median DOR was not reached (NR) (95% CI, 1.87 to NR; months). Treatment-emergent adverse events (TEAEs) were manageable. TEAEs that occurred in ≥20% of patients included thrombocytopenia, anemia, alopecia, dysgeusia, neutropenia, lymphopenia, leukopenia, decreased appetite, and pyrexia. Grade ≥3 TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia. Valemetostat demonstrated promising efficacy and tolerability in heavily pretreated patients, warranting further investigation in treating R/R ATL. This trial was registered at www.clinicaltrials.gov as #NCT04102150.</jats:p>
収録刊行物
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- Blood
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Blood 141 (10), 1159-1168, 2023-03-09
American Society of Hematology