Venetoclax plus 3 + 7 daunorubicin and cytarabine chemotherapy as first-line treatment for adults with acute myeloid leukaemia: a multicentre, single-arm, phase 2 trial.,The Lancet Haematology

当前位置： X-MOL 学术 › Lancet Haematol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Venetoclax plus 3 + 7 daunorubicin and cytarabine chemotherapy as first-line treatment for adults with acute myeloid leukaemia: a multicentre, single-arm, phase 2 trial.
The Lancet Haematology ( IF 15.4 ) Pub Date : 2022-05-02 , DOI: 10.1016/s2352-3026(22)00106-5
Huafeng Wang ₁ , Liping Mao ₂ , Min Yang ₂ , Pengxu Qian ₃ , Huan Lu ₄ , Hongyan Tong ₅ , Wanzhuo Xie ₅ , De Zhou ₂ , Xin Huang ₆ , Yungui Wang ₆ , Gaixiang Xu ₂ , Ying Lu ₇ , Juying Wei ₂ , Wenyuan Mai ₂ , Xiujin Ye ₈ , Haitao Meng ₅ , Yaojia Shen ₂ , Jian Huang ₉ , Wenjuan Yu ₅ , Jie Sun ₆ , Jianpeng Sheng ₁₀ , Xiaoyan Yan ₁₁ , Jie Jin ₅ , Hong-Hu Zhu ₁

Affiliation

Department of Haematology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Zhejiang Provincial Key Laboratory of Haematopoietic Malignancy, Zhejiang University, Hangzhou, Zhejiang, China; Zhejiang Provincial Clinical Research Center for Haematological Disorders, Hangzhou, Zhejiang, China; Zhejiang University Cancer Center, Hangzhou, Zhejiang, China; Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, Zhejiang, China.
Department of Haematology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Zhejiang Provincial Clinical Research Center for Haematological Disorders, Hangzhou, Zhejiang, China.
Zhejiang University Cancer Center, Hangzhou, Zhejiang, China; Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, Zhejiang, China; Center of Stem Cell and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, Zhejiang, China; Center of Stem Cell and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Department of Haematology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Zhejiang Provincial Key Laboratory of Haematopoietic Malignancy, Zhejiang University, Hangzhou, Zhejiang, China; Zhejiang Provincial Clinical Research Center for Haematological Disorders, Hangzhou, Zhejiang, China; Zhejiang University Cancer Center, Hangzhou, Zhejiang, China.
Zhejiang Provincial Key Laboratory of Haematopoietic Malignancy, Zhejiang University, Hangzhou, Zhejiang, China.
Department of Haematology, Affiliated People's Hospital of Ningbo University, Ningbo, China.
Department of Haematology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Zhejiang Provincial Key Laboratory of Haematopoietic Malignancy, Zhejiang University, Hangzhou, Zhejiang, China; Zhejiang Provincial Clinical Research Center for Haematological Disorders, Hangzhou, Zhejiang, China.
Department of Haematology, Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, China.
Zhejiang Provincial Key Laboratory of Pancreatic Disease, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Peking University Clinical Research Institute, Beijing, China.

BACKGROUND Adults with acute myeloid leukaemia have unsatisfactory clinical outcomes and rates of complete remission. Venetoclax combined with azacytidine or low-dose cytarabine has shown efficacy in adults aged 75 years or older (or 18-74 years with comorbidities precluding intensive chemotherapy) with acute myeloid leukaemia. We aimed to investigate the activity and safety of venetoclax plus 3+7 daunorubicin and cytarabine chemotherapy in adults with acute myeloid leukaemia. METHODS We conducted a two-stage, single-arm, phase 2 trial at three public hospitals in China. We enrolled patients aged 18-60 years with previously untreated de novo acute myeloid leukaemia and an Eastern Cooperative Oncology Group performance status of 0-2. Patients received induction treatment with intravenous daunorubicin (60 mg/m2 on days 1-3), intravenous cytarabine (100 mg/m2 on days 1-7), and oral venetoclax (100 mg on day 4, 200 mg on day 5, and 400 mg on days 6-11; DAV regimen). For induction therapy, the length of the treatment was 28-35 days per cycle and the number of treatment cycles was one or two. The primary endpoint was the composite complete remission rate (complete remission plus complete remission with incomplete blood cell count recovery) after one cycle of induction treatment, assessed in the as-treated population. Secondary endpoints were bone marrow measurable residual disease by flow cytometry, event-free survival, overall survival, and adverse events. This trial is ongoing and is registered with Chinese Clinical Trial Registry, ChiCTR2000041509. FINDINGS Between Dec 25, 2020, and July 7, 2021, 36 patients were assessed for eligibility and 33 were enrolled. 15 (45%) patients were men and 18 (55%) were women, and all were Asian. The composite complete remission rate after one cycle of DAV regimen was 91% (95% CI 76-98; 30 of 33 patients) in the entire cohort. 29 (97%) of 30 patients who reached complete remission had undetectable measurable residual disease (ie, <0·1%). Grade 3 or worse adverse events included neutropenia in 33 (100%) of 33 patients, thrombocytopenia in 33 (100%), anaemia in 33 (100%), febrile neutropenia in 18 (55%), pneumonia in seven (21%), and sepsis in four (12%). No treatment-related deaths occurred. With a median follow-up of 11 months (IQR 9-12), estimated 1-year overall survival was 97% (95% CI 91-100) and 1-year event-free survival was 72% (56-94). INTERPRETATION The DAV regimen represents an effective induction therapy for newly diagnosed adults with acute myeloid leukaemia, which resulted in a high rate of complete remission. These findings are an important contribution to the field, showing a safe strategy to incorporate venetoclax into the most common induction regimen used to treat newly diagnosed acute myeloid leukaemia internationally. FUNDING Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang, National Natural Science Foundation of China, Key Research and Development Program of Zhejiang. TRANSLATION For the Chinese translation of the abstract see Supplementary Materials section.

更新日期：2022-05-02

点击分享查看原文

点击收藏

阅读更多本刊最新论文