High efficacy of Azacitidine plus HAG in acute myeloid leukemia: an open-label, single-arm, multi-center, phase 2 study

Li, Jun; Han, Qi; Huang, Yanqing; Wei, Yanhui; Zi, Jian; Zhao, Li-Dong; Cai, Zhimei; Lu, Xuzhang; Xiao, Rong; Zhang, Yanming; Yang, Xiaotian; Hu, Xu; Sun, Naitong; Zhuang, Wanchuan; Wu, Zhengdong; Yuan, Xianglin; Xu, Yanli; He, Bin; Zhu, Wei; Min, Fengling; Chen, Yongchun; Ding, Banghe; Shi, Peimin; Xie, Jing; Tang, Hua; Liu, Zefa; Li, Bing‐Zong; Sun, Yu; Qiu, Hong-Xia; Duan, Limin; Dovat, Elanora; Song, Chunhua; SzeKely, Laszlo; Dovat, Sinisa; Ge, Zheng

doi:10.1038/s41408-022-00740-3

Cited by 4 publications

(8 citation statements)

References 14 publications

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“…Our recently published clinical trial demonstrated the promising therapeutic responses in elderly AML patients or ineligible for IC treated with Aza combined with HAG (HHT, low-dose cytarabine, G-CSF) (23). To our knowledge, this is the A previous study has reported that HHT-based regimens, including HDA (HHT, daunorubicin, cytarabine) and HAA (HHT, aclarubicin, cytarabine), benefit AML patients more rather than DA (daunorubicin, cytarabine, "3+7") regimen without increased toxicity (22).…”

Section: Discussionmentioning

confidence: 99%

“…Our recently published clinical trial demonstrated the promising therapeutic responses in elderly AML patients or ineligible for IC treated with Aza combined with HAG (HHT, low-dose cytarabine, G-CSF) ( 23 ). To our knowledge, this is the first clinical trial to evaluate the efficacy and safety of the combination of Aza and HIA regimen in young and/or older patients fit for IC.…”

Section: Discussionmentioning

confidence: 99%

“…It is reported that HHT in combination with cytarabine, aclarubicin/daunorubicin (HAA/HDA) achieved a higher CR rate than the standard “3+7” regimen (DA) in treating de novo AML ( 22 ). Our recently published clinical trial demonstrated promising therapeutic responses in elderly AML patients or ineligible for IC treated with Aza combined with HAG (HHT, low-dose cytarabine, G-CSF) ( 23 ). However, so far, it has not been well determined the efficacy and safety of adding Aza to the HHT-based regimen for young and/or older patients eligible for IC as the first-line inducting therapy.…”

Section: Introductionmentioning

confidence: 99%

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High efficacy of azacitidine combined with homoharringtonine, idarubicin, and cytarabine in newly diagnosed patients with AML: A single arm, phase 2 trial

Huang

Hou

et al. 2022

Front. Oncol.

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IntroductionThis study aims to evaluate the efficacy and safety of the novel combination of Aza and HIA as the frontline induction therapy in newly diagnosed AML patients eligible for intensive chemotherapy (IC) (registered on ClinicalTrials.gov, number NCT04248595).MethodsAza (75mg/m2/d on days1-5 subcutaneous) is administered in combination with HIA [HHT 2mg/m2/d on days 4-8 intravenous over 3 hours, idarubicin 6mg/m2/d on days 4-6 intravenous, and cytarabine 100mg/m2/d on days 4-10 intravenous]. The primary endpoint was complete remission (CR) or CR with incomplete blood count recovery (CRi). Secondary endpoints were overall survival (OS), relapse-free survival (RFS), and adverse events (AEs).ResultsA total of 20 AML patients (aged 18-70 years) were enrolled between Jan 2020 and Sep 2022. 95% (19/20) of patients achieved CR/CRi, and 89.5% (17/19) had undetectable MRD, in which 94.7% (18/19) reached CR/CRi, and 88.9% (16/18) obtained MRD negative after the 1st cycle of induction therapy. Median OS and RFS were both not reached during the follow-up. The estimated 2-year OS and RFS were 87.5% (95%CI, 58.6% to 96.7%) and 87.1% (95%CI, 57.3% to 96.6%), respectively. No patient discontinued the treatment for AEs.DiscussionThis study provides preliminary evidence for this novel combination therapy as the first-line induction therapy for young or older AML patients fit for IC.

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Section: Discussionmentioning

confidence: 99%

“…Our recently published clinical trial demonstrated the promising therapeutic responses in elderly AML patients or ineligible for IC treated with Aza combined with HAG (HHT, low-dose cytarabine, G-CSF) ( 23 ). To our knowledge, this is the first clinical trial to evaluate the efficacy and safety of the combination of Aza and HIA regimen in young and/or older patients fit for IC.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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High efficacy of azacitidine combined with homoharringtonine, idarubicin, and cytarabine in newly diagnosed patients with AML: A single arm, phase 2 trial

Huang

Hou

et al. 2022

Front. Oncol.

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“…Mounting evidence has shown that CAG-based regimens are associated with a remission rate of approximately 60% and low toxicity. 7,8 However, a comparison of the outcomes of these two regimens has not been reported. In this study, we performed a multicenter, retrospective propensity score-matched study to compare the therapeutic responses and survival outcomes of patients with newly diagnosed AML who underwent induction therapy with VEN/HMA to those who received CAG-based treatments.…”

Section: Introductionmentioning

confidence: 99%

Venetoclax plus a hypomethylating agent versus cytarabine, aclarubicin, and granulocyte colony‐stimulating factor chemotherapy as a first‐line therapy for newly diagnosed acute myeloid leukemia: A propensity score–matched analysis

Huang,

He,

et al. 2024

Cancer

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BackgroundBoth venetoclax plus a hypomethylating agent (VEN/HMA) and cytarabine, aclarubicin, and granulocyte colony‐stimulating factor (CAG) are low‐intensity regimens for older patients with acute myeloid leukemia (AML) that show good efficacy and safety. It is unknown how VEN/HMA compares with the CAG regimen for the treatment of newly diagnosed AML.MethodsThe outcomes of patients with newly diagnosed AML treated with VEN/HMA were compared with those of patients treated with a CAG‐based regimen. Propensity score matching between these two cohorts at a 1:1 ratio was performed according to age at diagnosis, sex, Eastern Cooperative Oncology Group performance status, state of fitness, and European LeukemiaNet (ELN) 2022 risk stratification to minimize bias.ResultsA total of 84 of 96 patients in the VEN/HMA cohort were matched with 84 of 147 patients in the CAG cohort. VEN/HMA resulted in a better response than the CAG‐based regimens, as indicated by a higher composite complete remission (CRc) rate (82.1% vs. 60.7%; p = .002) and minimal residual disease negativity rate (88.2% vs. 68.2%; p = .009). In patients with an ELN adverse risk, VEN/HMA was associated with a higher CRc rate compared to CAG (80.5% vs. 58.3%; p = .006). VEN/HMA was associated with longer event‐free survival (EFS) (median EFS, not reached vs. 4.5 months; p = .0004), whereas overall survival (OS) was comparable between the two cohorts (median OS, not reached vs. 18 months; p = .078).ConclusionsThe VEN/HMA regimen may result in a better response than CAG‐based treatment in older patients with newly diagnosed AML.

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“…Acute myeloid leukemia (AML) is a devastating hematologic malignancy characterized by a group of clonal diseases with high heterogeneity, and its incidence has increased with age in recent years [ 1 , 2 , 3 , 4 ]. Only 35% to 40% of adult AML patients younger than 60, while only 5% to 15% of AML patients over 60 experienced clinical remissions [ 5 , 6 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Azacitidine Is Synergistically Lethal with XPO1 Inhibitor Selinexor in Acute Myeloid Leukemia by Targeting XPO1/eIF4E/c-MYC Signaling

Long

Hou

et al. 2023

IJMS

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Acute myeloid leukemia (AML) is a high-mortality malignancy with poor outcomes. Azacitidine induces cell death and demonstrates treatment effectiveness against AML. Selinexor (KPT-330) exhibited significant benefits in combination with typical induction treatment for AML patients. Here, we explore the antitumor effect of KPT-330 combined with AZA in AML through CCK-8, flow cytometry, RT-qPCR, western blot, and RNA-seq. Our results showed that KPT-330 combined with AZA synergistically reduced cell proliferation and induced apoptosis in AML primary cells and cell lines. Compared to the control, the KPT-330 plus AZA down-regulates the expression of XPO1, eIF4E, and c-MYC in AML. Moreover, the knockdown of c-MYC could sensitize the synergy of the combination on suppression of cell proliferation and promotion of apoptosis in AML. Moreover, the expression of XPO1 and eIF4E was elevated in AML patient cohorts, respectively. XPO1 and elF4E overexpression was associated with poor prognosis. In summary, KPT-330 with AZA exerted synergistic effects by suppressing XPO1/eIF4E/c-MYC signaling, which provided preclinical evidence for further clinical application of the novel combination in AML.

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High efficacy of Azacitidine plus HAG in acute myeloid leukemia: an open-label, single-arm, multi-center, phase 2 study

Cited by 4 publications

References 14 publications

High efficacy of azacitidine combined with homoharringtonine, idarubicin, and cytarabine in newly diagnosed patients with AML: A single arm, phase 2 trial

High efficacy of azacitidine combined with homoharringtonine, idarubicin, and cytarabine in newly diagnosed patients with AML: A single arm, phase 2 trial

Venetoclax plus a hypomethylating agent versus cytarabine, aclarubicin, and granulocyte colony‐stimulating factor chemotherapy as a first‐line therapy for newly diagnosed acute myeloid leukemia: A propensity score–matched analysis

Azacitidine Is Synergistically Lethal with XPO1 Inhibitor Selinexor in Acute Myeloid Leukemia by Targeting XPO1/eIF4E/c-MYC Signaling

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