Cargando…
Venetoclax combined with daunorubicin and cytarabine (2 + 6) as induction treatment in adults with newly diagnosed acute myeloid leukemia: a phase 2, multicenter, single-arm trial
BACKGROUND: Venetoclax (Ven) combined with intensive chemotherapy was proven effective in the management of acute myeloid leukemia (AML). However, the severe and prolonged myelosuppression remains a concern to worry about. To explore more appropriate combination regimens, we designed Ven combining d...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10176670/ https://www.ncbi.nlm.nih.gov/pubmed/37173750 http://dx.doi.org/10.1186/s40164-023-00409-y |
_version_ | 1785040475785265152 |
---|---|
author | Suo, Xiaohui Zheng, Fang Wang, Dongmei Zhao, Liyun Liu, Jie Li, Ling Zhang, Zhihua Zhang, Congcong Li, Yinling Yang, Sisi Zhao, Xuemei Shi, Rui Wu, Yan Jiao, Zongjiu Song, Jiaojie Zhang, Ling Lu, Xinxiao Yuan, Linyu Gao, Sifeng Zhang, Jilei Zhao, Xingli Bai, Guanchen Liu, Kaiqi Mi, Yingchang |
author_facet | Suo, Xiaohui Zheng, Fang Wang, Dongmei Zhao, Liyun Liu, Jie Li, Ling Zhang, Zhihua Zhang, Congcong Li, Yinling Yang, Sisi Zhao, Xuemei Shi, Rui Wu, Yan Jiao, Zongjiu Song, Jiaojie Zhang, Ling Lu, Xinxiao Yuan, Linyu Gao, Sifeng Zhang, Jilei Zhao, Xingli Bai, Guanchen Liu, Kaiqi Mi, Yingchang |
author_sort | Suo, Xiaohui |
collection | PubMed |
description | BACKGROUND: Venetoclax (Ven) combined with intensive chemotherapy was proven effective in the management of acute myeloid leukemia (AML). However, the severe and prolonged myelosuppression remains a concern to worry about. To explore more appropriate combination regimens, we designed Ven combining daunorubicin and cytarabine (DA 2 + 6) regimen as induction therapy, aimed to evaluate the effectiveness and safety in adults de novo AML. METHODS: A phase 2 clinical trial was performed in 10 Chinese hospitals to investigate Ven combined with daunorubicin and cytarabine (DA 2 + 6) in patients with AML. The primary endpoints were overall response rate (ORR), comprising of complete remission (CR), complete remission with incomplete blood cell count recovery (CRi), and partial response (PR). Secondary endpoints included measurable residual disease (MRD) of bone marrow assessed by flow cytometry, overall survival (OS), event-free survival (EFS), disease-free survival (DFS), and the safety of regimens. This study is a currently ongoing trial listed on the Chinese Clinical Trial Registry as ChiCTR2200061524. RESULTS: Overall, 42 patients were enrolled from January 2022 to November 2022; 54.8% (23/42) were male, and the median age was 40 (range, 16–60) years. The ORR after one cycle of induction was 92.9% (95% confidence interval [CI], 91.6–94.1; 39/42) with a composite complete response rate (CR + CRi) 90.5% (95% CI, 89.3–91.6, CR 37/42, CRi 1/42). Moreover, 87.9% (29/33) of the CR patients with undetectable MRD (95% CI, 84.9–90.8). Grade 3 or worse adverse effects included neutropenia (100%), thrombocytopenia (100%), febrile neutropenia (90.5%), and one mortality. The median neutrophil and platelet recovery times were 13 (5–26) and 12 (8–26) days, respectively. Until Jan 30, 2023, the estimated 12-month OS, EFS, and DFS rates were 83.1% (95% CI, 78.8–87.4), 82.7% (95% CI, 79.4–86.1), and 92.0% (95% CI, 89.8–94.3), respectively. CONCLUSION: Ven with DA (2 + 6) is a highly effective and safe induction therapy for adults with newly diagnosed AML. To the best of our knowledge, this induction therapy has the shortest myelosuppressive period but has similar efficacy to previous studies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40164-023-00409-y. |
format | Online Article Text |
id | pubmed-10176670 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-101766702023-05-13 Venetoclax combined with daunorubicin and cytarabine (2 + 6) as induction treatment in adults with newly diagnosed acute myeloid leukemia: a phase 2, multicenter, single-arm trial Suo, Xiaohui Zheng, Fang Wang, Dongmei Zhao, Liyun Liu, Jie Li, Ling Zhang, Zhihua Zhang, Congcong Li, Yinling Yang, Sisi Zhao, Xuemei Shi, Rui Wu, Yan Jiao, Zongjiu Song, Jiaojie Zhang, Ling Lu, Xinxiao Yuan, Linyu Gao, Sifeng Zhang, Jilei Zhao, Xingli Bai, Guanchen Liu, Kaiqi Mi, Yingchang Exp Hematol Oncol Research BACKGROUND: Venetoclax (Ven) combined with intensive chemotherapy was proven effective in the management of acute myeloid leukemia (AML). However, the severe and prolonged myelosuppression remains a concern to worry about. To explore more appropriate combination regimens, we designed Ven combining daunorubicin and cytarabine (DA 2 + 6) regimen as induction therapy, aimed to evaluate the effectiveness and safety in adults de novo AML. METHODS: A phase 2 clinical trial was performed in 10 Chinese hospitals to investigate Ven combined with daunorubicin and cytarabine (DA 2 + 6) in patients with AML. The primary endpoints were overall response rate (ORR), comprising of complete remission (CR), complete remission with incomplete blood cell count recovery (CRi), and partial response (PR). Secondary endpoints included measurable residual disease (MRD) of bone marrow assessed by flow cytometry, overall survival (OS), event-free survival (EFS), disease-free survival (DFS), and the safety of regimens. This study is a currently ongoing trial listed on the Chinese Clinical Trial Registry as ChiCTR2200061524. RESULTS: Overall, 42 patients were enrolled from January 2022 to November 2022; 54.8% (23/42) were male, and the median age was 40 (range, 16–60) years. The ORR after one cycle of induction was 92.9% (95% confidence interval [CI], 91.6–94.1; 39/42) with a composite complete response rate (CR + CRi) 90.5% (95% CI, 89.3–91.6, CR 37/42, CRi 1/42). Moreover, 87.9% (29/33) of the CR patients with undetectable MRD (95% CI, 84.9–90.8). Grade 3 or worse adverse effects included neutropenia (100%), thrombocytopenia (100%), febrile neutropenia (90.5%), and one mortality. The median neutrophil and platelet recovery times were 13 (5–26) and 12 (8–26) days, respectively. Until Jan 30, 2023, the estimated 12-month OS, EFS, and DFS rates were 83.1% (95% CI, 78.8–87.4), 82.7% (95% CI, 79.4–86.1), and 92.0% (95% CI, 89.8–94.3), respectively. CONCLUSION: Ven with DA (2 + 6) is a highly effective and safe induction therapy for adults with newly diagnosed AML. To the best of our knowledge, this induction therapy has the shortest myelosuppressive period but has similar efficacy to previous studies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40164-023-00409-y. BioMed Central 2023-05-12 /pmc/articles/PMC10176670/ /pubmed/37173750 http://dx.doi.org/10.1186/s40164-023-00409-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Suo, Xiaohui Zheng, Fang Wang, Dongmei Zhao, Liyun Liu, Jie Li, Ling Zhang, Zhihua Zhang, Congcong Li, Yinling Yang, Sisi Zhao, Xuemei Shi, Rui Wu, Yan Jiao, Zongjiu Song, Jiaojie Zhang, Ling Lu, Xinxiao Yuan, Linyu Gao, Sifeng Zhang, Jilei Zhao, Xingli Bai, Guanchen Liu, Kaiqi Mi, Yingchang Venetoclax combined with daunorubicin and cytarabine (2 + 6) as induction treatment in adults with newly diagnosed acute myeloid leukemia: a phase 2, multicenter, single-arm trial |
title | Venetoclax combined with daunorubicin and cytarabine (2 + 6) as induction treatment in adults with newly diagnosed acute myeloid leukemia: a phase 2, multicenter, single-arm trial |
title_full | Venetoclax combined with daunorubicin and cytarabine (2 + 6) as induction treatment in adults with newly diagnosed acute myeloid leukemia: a phase 2, multicenter, single-arm trial |
title_fullStr | Venetoclax combined with daunorubicin and cytarabine (2 + 6) as induction treatment in adults with newly diagnosed acute myeloid leukemia: a phase 2, multicenter, single-arm trial |
title_full_unstemmed | Venetoclax combined with daunorubicin and cytarabine (2 + 6) as induction treatment in adults with newly diagnosed acute myeloid leukemia: a phase 2, multicenter, single-arm trial |
title_short | Venetoclax combined with daunorubicin and cytarabine (2 + 6) as induction treatment in adults with newly diagnosed acute myeloid leukemia: a phase 2, multicenter, single-arm trial |
title_sort | venetoclax combined with daunorubicin and cytarabine (2 + 6) as induction treatment in adults with newly diagnosed acute myeloid leukemia: a phase 2, multicenter, single-arm trial |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10176670/ https://www.ncbi.nlm.nih.gov/pubmed/37173750 http://dx.doi.org/10.1186/s40164-023-00409-y |
work_keys_str_mv | AT suoxiaohui venetoclaxcombinedwithdaunorubicinandcytarabine26asinductiontreatmentinadultswithnewlydiagnosedacutemyeloidleukemiaaphase2multicentersinglearmtrial AT zhengfang venetoclaxcombinedwithdaunorubicinandcytarabine26asinductiontreatmentinadultswithnewlydiagnosedacutemyeloidleukemiaaphase2multicentersinglearmtrial AT wangdongmei venetoclaxcombinedwithdaunorubicinandcytarabine26asinductiontreatmentinadultswithnewlydiagnosedacutemyeloidleukemiaaphase2multicentersinglearmtrial AT zhaoliyun venetoclaxcombinedwithdaunorubicinandcytarabine26asinductiontreatmentinadultswithnewlydiagnosedacutemyeloidleukemiaaphase2multicentersinglearmtrial AT liujie venetoclaxcombinedwithdaunorubicinandcytarabine26asinductiontreatmentinadultswithnewlydiagnosedacutemyeloidleukemiaaphase2multicentersinglearmtrial AT liling venetoclaxcombinedwithdaunorubicinandcytarabine26asinductiontreatmentinadultswithnewlydiagnosedacutemyeloidleukemiaaphase2multicentersinglearmtrial AT zhangzhihua venetoclaxcombinedwithdaunorubicinandcytarabine26asinductiontreatmentinadultswithnewlydiagnosedacutemyeloidleukemiaaphase2multicentersinglearmtrial AT zhangcongcong venetoclaxcombinedwithdaunorubicinandcytarabine26asinductiontreatmentinadultswithnewlydiagnosedacutemyeloidleukemiaaphase2multicentersinglearmtrial AT liyinling venetoclaxcombinedwithdaunorubicinandcytarabine26asinductiontreatmentinadultswithnewlydiagnosedacutemyeloidleukemiaaphase2multicentersinglearmtrial AT yangsisi venetoclaxcombinedwithdaunorubicinandcytarabine26asinductiontreatmentinadultswithnewlydiagnosedacutemyeloidleukemiaaphase2multicentersinglearmtrial AT zhaoxuemei venetoclaxcombinedwithdaunorubicinandcytarabine26asinductiontreatmentinadultswithnewlydiagnosedacutemyeloidleukemiaaphase2multicentersinglearmtrial AT shirui venetoclaxcombinedwithdaunorubicinandcytarabine26asinductiontreatmentinadultswithnewlydiagnosedacutemyeloidleukemiaaphase2multicentersinglearmtrial AT wuyan venetoclaxcombinedwithdaunorubicinandcytarabine26asinductiontreatmentinadultswithnewlydiagnosedacutemyeloidleukemiaaphase2multicentersinglearmtrial AT jiaozongjiu venetoclaxcombinedwithdaunorubicinandcytarabine26asinductiontreatmentinadultswithnewlydiagnosedacutemyeloidleukemiaaphase2multicentersinglearmtrial AT songjiaojie venetoclaxcombinedwithdaunorubicinandcytarabine26asinductiontreatmentinadultswithnewlydiagnosedacutemyeloidleukemiaaphase2multicentersinglearmtrial AT zhangling venetoclaxcombinedwithdaunorubicinandcytarabine26asinductiontreatmentinadultswithnewlydiagnosedacutemyeloidleukemiaaphase2multicentersinglearmtrial AT luxinxiao venetoclaxcombinedwithdaunorubicinandcytarabine26asinductiontreatmentinadultswithnewlydiagnosedacutemyeloidleukemiaaphase2multicentersinglearmtrial AT yuanlinyu venetoclaxcombinedwithdaunorubicinandcytarabine26asinductiontreatmentinadultswithnewlydiagnosedacutemyeloidleukemiaaphase2multicentersinglearmtrial AT gaosifeng venetoclaxcombinedwithdaunorubicinandcytarabine26asinductiontreatmentinadultswithnewlydiagnosedacutemyeloidleukemiaaphase2multicentersinglearmtrial AT zhangjilei venetoclaxcombinedwithdaunorubicinandcytarabine26asinductiontreatmentinadultswithnewlydiagnosedacutemyeloidleukemiaaphase2multicentersinglearmtrial AT zhaoxingli venetoclaxcombinedwithdaunorubicinandcytarabine26asinductiontreatmentinadultswithnewlydiagnosedacutemyeloidleukemiaaphase2multicentersinglearmtrial AT baiguanchen venetoclaxcombinedwithdaunorubicinandcytarabine26asinductiontreatmentinadultswithnewlydiagnosedacutemyeloidleukemiaaphase2multicentersinglearmtrial AT liukaiqi venetoclaxcombinedwithdaunorubicinandcytarabine26asinductiontreatmentinadultswithnewlydiagnosedacutemyeloidleukemiaaphase2multicentersinglearmtrial AT miyingchang venetoclaxcombinedwithdaunorubicinandcytarabine26asinductiontreatmentinadultswithnewlydiagnosedacutemyeloidleukemiaaphase2multicentersinglearmtrial |