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An open-label, single-arm phase 2 trial of valemetostat for relapsed or refractory adult T-cell leukemia/lymphoma
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,...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society of Hematology
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10651775/ https://www.ncbi.nlm.nih.gov/pubmed/36150143 http://dx.doi.org/10.1182/blood.2022016862 |
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author | Izutsu, Koji Makita, Shinichi Nosaka, Kisato Yoshimitsu, Makoto Utsunomiya, Atae Kusumoto, Shigeru Morishima, Satoko Tsukasaki, Kunihiro Kawamata, Toyotaka Ono, Takaaki Rai, Shinya Katsuya, Hiroo Ishikawa, Jun Yamada, Hironori Kato, Kazunobu Tachibana, Masaya Kakurai, Yasuyuki Adachi, Nobuaki Tobinai, Kensei Yonekura, Kentaro Ishitsuka, Kenji |
author_facet | Izutsu, Koji Makita, Shinichi Nosaka, Kisato Yoshimitsu, Makoto Utsunomiya, Atae Kusumoto, Shigeru Morishima, Satoko Tsukasaki, Kunihiro Kawamata, Toyotaka Ono, Takaaki Rai, Shinya Katsuya, Hiroo Ishikawa, Jun Yamada, Hironori Kato, Kazunobu Tachibana, Masaya Kakurai, Yasuyuki Adachi, Nobuaki Tobinai, Kensei Yonekura, Kentaro Ishitsuka, Kenji |
author_sort | Izutsu, Koji |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10651775 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The American Society of Hematology |
record_format | MEDLINE/PubMed |
spelling | pubmed-106517752022-09-27 An open-label, single-arm phase 2 trial of valemetostat for relapsed or refractory adult T-cell leukemia/lymphoma Izutsu, Koji Makita, Shinichi Nosaka, Kisato Yoshimitsu, Makoto Utsunomiya, Atae Kusumoto, Shigeru Morishima, Satoko Tsukasaki, Kunihiro Kawamata, Toyotaka Ono, Takaaki Rai, Shinya Katsuya, Hiroo Ishikawa, Jun Yamada, Hironori Kato, Kazunobu Tachibana, Masaya Kakurai, Yasuyuki Adachi, Nobuaki Tobinai, Kensei Yonekura, Kentaro Ishitsuka, Kenji Blood Clinical Trials and Observations 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. The American Society of Hematology 2023-03-09 2022-09-27 /pmc/articles/PMC10651775/ /pubmed/36150143 http://dx.doi.org/10.1182/blood.2022016862 Text en © 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Clinical Trials and Observations Izutsu, Koji Makita, Shinichi Nosaka, Kisato Yoshimitsu, Makoto Utsunomiya, Atae Kusumoto, Shigeru Morishima, Satoko Tsukasaki, Kunihiro Kawamata, Toyotaka Ono, Takaaki Rai, Shinya Katsuya, Hiroo Ishikawa, Jun Yamada, Hironori Kato, Kazunobu Tachibana, Masaya Kakurai, Yasuyuki Adachi, Nobuaki Tobinai, Kensei Yonekura, Kentaro Ishitsuka, Kenji An open-label, single-arm phase 2 trial of valemetostat for relapsed or refractory adult T-cell leukemia/lymphoma |
title | An open-label, single-arm phase 2 trial of valemetostat for relapsed or refractory adult T-cell leukemia/lymphoma |
title_full | An open-label, single-arm phase 2 trial of valemetostat for relapsed or refractory adult T-cell leukemia/lymphoma |
title_fullStr | An open-label, single-arm phase 2 trial of valemetostat for relapsed or refractory adult T-cell leukemia/lymphoma |
title_full_unstemmed | An open-label, single-arm phase 2 trial of valemetostat for relapsed or refractory adult T-cell leukemia/lymphoma |
title_short | An open-label, single-arm phase 2 trial of valemetostat for relapsed or refractory adult T-cell leukemia/lymphoma |
title_sort | open-label, single-arm phase 2 trial of valemetostat for relapsed or refractory adult t-cell leukemia/lymphoma |
topic | Clinical Trials and Observations |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10651775/ https://www.ncbi.nlm.nih.gov/pubmed/36150143 http://dx.doi.org/10.1182/blood.2022016862 |
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