Welcome to PracticeUpdate! We hope you are enjoying access to a selection of our top-read and most recent articles. Please register today for a free account and gain full access to all of our expert-selected content.
Already Have An Account? Log in Now
Venetoclax Plus Daunorubicin and Cytarabine Chemotherapy as First-Line Treatment for Adults With AML
TAKE-HOME MESSAGE
- This two-stage, single-arm, phase II study evaluated the use of venetoclax in combination with standard daunorubicin and cytarabine chemotherapy in patients with untreated de novo acute myeloid leukaemia (AML). The combined regimen achieved a complete remission rate of 91%, with minimal residual disease negativity of 97%. With a short median follow-up of 11 months, the 1-year survival, disease-free survival, and event-free survival rates were 97%, 80%, and 72%, respectively. Grades 3 to 4 haematological and non-haematological adverse effects were observed; however, the duration of myelosuppression was shorter than that with other regimens. There was no treatment-associated mortality.
- Although randomised controlled trials are needed to validate these findings, the addition of venetoclax to a standard daunorubicin and cytarabine induction regimen should be considered for induction therapy in patients newly diagnosed with AML.
abstract
This abstract is available on the publisher's site.
Access this abstract now Full Text Available for ClinicalKey SubscribersBACKGROUND
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.
Additional Info
Disclosure statements are available on the authors' profiles:
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
Lancet Haematol 2022 May 02;[EPub Ahead of Print], H Wang, L Mao, M Yang, P Qian, H Lu, H Tong, W Xie, Zhou, X Huang, Y Wang, G Xu, Y Lu, J Wei, W Mai, X Ye, H Meng, Y Shen, J Huang, W Yu, J Sun, J Sheng, X Yan, J Jin, HH ZhuFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
This study by Wang et al adds to the growing body of evidence that venetoclax, which has transformed the care of patients with acute myelogenous leukaemia (AML) deemed suitable for low-intensity therapy, may also play an important role in enhancing the efficacy of intensive chemotherapy in eligible patients. Mindful of the risk of prolonged cytopenias, the authors designed this study to include just 8 days of venetoclax therapy (a cumulative dose of 2700 mg, which is less than what has been used in other intensive therapy studies employing venetoclax) in combination with the conventional DA regimen—that is, 7 + 3 cytarabine (100 mg/m2 on days 1–7) and daunorubicin (60 mg/m2 on days 1–3)—in patients aged 18 to 60 years with untreated de novo AML. This DAV regimen was associated with a complete remission (CR) rate of 91%, with 97% of the patients who reached CR achieving a disease burden <0.1% (deemed MRD negative). The short course of venetoclax, while appearing likely to be associated with improved CR rates compared with those of historical 7 + 3 cohorts, did not prolong count recovery, with a median of 21 days to neutrophil and platelet recovery. These findings compare favourably with results from other studies adding venetoclax to intensive chemotherapy (eg, FLAG-IDA+venetoclax and CLIA+venetoclax). The DAV regimen led to an impressive 1-year survival rate of 97%, with 80% disease-free survival. These extremely encouraging results serve as the basis for an ongoing larger study randomising between the DA and DAV regimens.