The efficacy and adverse events of venetoclax in combination with hypomethylating agents treatment for patients with acute myeloid leukemia and myelodysplastic syndrome: a systematic review and meta-analysis

Liu, Bei; Guo, Yuancheng; Deng, Lijuan; Qiao, Yi; Jian, Jinli

doi:10.1080/16078454.2020.1843752

Cited by 24 publications

(6 citation statements)

References 22 publications

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“…Venetoclax (VEN) is a potent inhibitor of anti-apoptotic B-cell leukemia/lymphoma-2 (BCL-2) which is overexpressed in leukemia stem cells [ 1 , 2 ] Clinical data have demonstrated that VEN-based combination chemotherapy with hypomethylating agents (HMAs) or low-dose cytarabine (LDAC) leads to more desirable outcomes than HMAs or LDAC alone in patients with acute myeloid leukemia (AML) [ 3 , 4 , 5 , 6 ]. Recently, a VEN-based combination with HMAs or LDAC has been approved for the treatment of newly diagnosed (ND) elderly AML patients and has emerged as a promising therapeutic option for relapsed/refractory (R/R) AML as well [ 3 , 7 , 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Infections of Venetoclax-Based Chemotherapy in Acute Myeloid Leukemia: Rationale for Proper Antimicrobial Prophylaxis

Lee

Cho

Lee

et al. 2021

Cancers

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Although venetoclax (VEN)-based combination chemotherapy in patients with acute myeloid leukemia (AML) results in prolonged and profound neutropenia, data regarding infectious complications and antimicrobial prophylaxis are lacking. We investigated the infectious complications in 122 adult patients with AML under the same standard of care for prevention. The prophylaxis protocol was fluconazole 400 mg/d without antibacterial agents. The incidence of proven or probable invasive fungal infections (IFIs) was 6.6/100 cycles, and 22 patients (18.0%) were diagnosed (median, second cycle; interquartile range, 1–2). All IFIs were caused by Aspergillus and significantly influenced the overall mortality (odds ratio (OR), 2.737; 95% confidence interval (CI), 1.051–7.128; p = 0.034). In the multivariate analysis, secondary or therapy-related AML was an independent risk factor for IFIs (OR, 3.859; 95% CI, 1.344–11.048, p = 0.012). A total of 39 bloodstream infection (BSIs) episodes occurred in 35 patients (28.7%), with an incidence of 12.7/100 cycles. High-dose steroid administration within 90 days was associated with the occurrence of BSIs (OR, 7.474; 95% CI; 1.661–3.631, p = 0.008), although BSIs themselves did not have an impact on the outcomes. Our findings suggest evidence for the need for mold-active antifungal agents as antifungal prophylaxis, rather than fluconazole, especially in patients with secondary or therapy-related AML.

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Section: Introductionmentioning

confidence: 99%

Infections of Venetoclax-Based Chemotherapy in Acute Myeloid Leukemia: Rationale for Proper Antimicrobial Prophylaxis

Lee

Cho

Lee

et al. 2021

Cancers

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“…In the lower-intensity regimens with the addition of venetoclax, the most common grade 3/4 adverse events were infections and cytopenias. The febrile neutropenia occurs in 47%, grade 3/4 decrease of white blood cells in 42%, grade 3/4 anemia in 28%, and grade 3/4 thrombocytopenia in 33% [32]. In the case of IC + venetoclax treatment in newly diagnosed AML, the grade 3/4 adverse events included febrile neutropenia (39-55%), pneumonia (24-28%), bacteremia (21%) and sepsis (10%) [29,30,33].…”

Section: Clinical Data For Venetoclaxmentioning

confidence: 99%

AML under the Scope: Current Strategies and Treatment Involving FLT3 Inhibitors and Venetoclax-Based Regimens

Milnerowicz,

Maszewska,

Skowera

et al. 2023

IJMS

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Acute myeloid leukemia (AML) is a disease that mainly affects elderly patients who are more often unfit for intensive chemotherapy (median age of diagnosis is 68). The regimens, including venetoclax, a highly specific BCL-2 (B-cell lymphoma-2) inhibitor, are a common alternative because of their safer profile and fewer side effects. However, the resistance phenomenon of leukemic cells necessitates the search for drugs that would help to overcome the resistance and improve treatment outcomes. One of the resistance mechanisms takes place through the upregulation of MCL-1 and BCL-XL, preventing BAX/BAK-driven MOMP (mitochondrial outer membrane permeabilization), thus stopping the apoptosis process. Possible partners for BCL-2 inhibitors may include inhibitors from the FLT3i (FMS-like tyrosine kinase-3 inhibitor) group. They resensitize cancer cells through the downregulation of MCL-1 expression in the FLT3 mutated cells, resulting in the stronger efficacy of BCL-2 inhibitors. Also, they provide an additional pathway for targeting the clonal cell. Both preclinical and clinical data suggest that the combination might show a synergistic effect and improve patients’ outcomes. The aim of this review is to determine whether the combination of venetoclax and FLT3 inhibitors can impact the therapeutic approaches and what other agents they can be combined with.

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“…The findings highlight that the incorporation of venetoclax in addition to traditional hypomethylating agents in the treatment of MDS may yield significant clinical benefits. However, the review also noted a possible enhanced risk of developing febrile neutropenia [ 32 , 36 ].…”

Section: Reviewmentioning

confidence: 99%

Myelodysplastic Syndromes and Modalities of Treatment: An Updated Literature Review

Zamora¹,

Patel²,

Grossmann³

et al. 2021

Cureus

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The efficacy and adverse events of venetoclax in combination with hypomethylating agents treatment for patients with acute myeloid leukemia and myelodysplastic syndrome: a systematic review and meta-analysis

Cited by 24 publications

References 22 publications

Infections of Venetoclax-Based Chemotherapy in Acute Myeloid Leukemia: Rationale for Proper Antimicrobial Prophylaxis

Infections of Venetoclax-Based Chemotherapy in Acute Myeloid Leukemia: Rationale for Proper Antimicrobial Prophylaxis

AML under the Scope: Current Strategies and Treatment Involving FLT3 Inhibitors and Venetoclax-Based Regimens

Myelodysplastic Syndromes and Modalities of Treatment: An Updated Literature Review

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