Hypomethylating Agents as a Therapy for AML

Gardin, Claude; Dombret, Hervé

doi:10.1007/s11899-017-0363-4

Cited by 51 publications

(45 citation statements)

References 94 publications

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“…The ORR was 68%, with response rates of 76% (decitabine) and 68% (azacitidine) in patients who received 400 mg venetoclax as compared to 71% (decitabine) and 60% (azacitidine) in patients who received 800 mg venetoclax, respectively. OS was estimated to be 79% at 6 months and 70% at 12 months, with the median not reached, which compares favourably to published data (Dombret et al , ; Gardin & Dombret, ). The safety profile was excellent, with mostly haematological adverse events.…”

Section: Pro‐apoptotic Agentssupporting

confidence: 87%

Advances in targeted therapy for acute myeloid leukaemia

2017

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In the past few years, research in the underlying pathogenic mechanisms of acute myeloid leukaemia (AML) has led to remarkable advances in our understanding of the disease. Cytogenetic and molecular aberrations are the most important factors in determining response to chemotherapy as well as long-term outcome, but beyond prognostication are potential therapeutic targets. Our increased understanding of the pathogenesis of AML, facilitated by next-generation sequencing, has spurred the development of new compounds in the treatment of AML, particularly the creation of small molecules that target the disease on a molecular level. Various new agents, such as tyrosine kinase inhibitors, immune checkpoint inhibitors, monoclonal or bispecific T-cell engager antibodies, metabolic and pro-apoptotic agents are currently investigated within clinical trials. The highest response rates are often achieved when new molecularly targeted therapies are combined with standard chemotherapy. Presented here is an overview of novel therapies currently being evaluated in AML.

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Section: Pro‐apoptotic Agentssupporting

confidence: 87%

Advances in targeted therapy for acute myeloid leukaemia

2017

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“…Decitabine (DAC, 5-aza-2′-deoxycytidine) is a hypomethylating drug currently used for the treatment of myelodisplastic syndrome and is currently gaining much attention for its use in other forms of blood cancer, including acute myeloblastic leukemia (Gardin and Dombret, 2017;Sato et al, 2017), as well as solid cancer (Linnekamp et al, 2017). Recent studies have also shown that DAC possesses potent immunomodulatory properties through different pharmacological mechanisms, that entail induction of regulatory T cells and shift of the Th1-Th17/Th2 cytokine balance, in favor of the latter, with consequential promotion of an anti-inflammatory mileau.…”

Section: Introductionmentioning

confidence: 99%

Decitabine induces regulatory T cells, inhibits the production of IFN-gamma and IL-17 and exerts preventive and therapeutic efficacy in rodent experimental autoimmune neuritis

Fagone

Mazzon

Chikovani

et al. 2018

Journal of Neuroimmunology

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Guillain-Barré syndrome (GBS) is an immune-mediated acute disorder of the peripheral nervous system. Despite treatment, there is an associated mortality and severe disability in 9 to 17% of the cases. Decitabine (DAC) is a hypomethylating drug used in myelodisplastic syndrome, that has been shown to exert immunomodulatory effects. We have evaluated the effects of DAC in two rodent models of GBS, the Experimental Allergic Neuritis (EAN). Both prophylactic and therapeutic treatment with DAC ameliorated the clinical course of EAN, increasing the numbers of thymic regulatory T cells and reducing the production of proinflammmatory cytokines. Our data suggest the possible use of decitabine for the treatment of GBS.

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“…In the last two decades, several new drugs have been investigated to address the need for delivering effective treatment even to those older patients with AML who are considered unfit for standard chemotherapy. Among them, hypomethylating agents (HMAs), with an overall response rate of 25-30%, have become the standard of care for the treatment of older patients with AML (aged ≥60 years) and for those who are considered ineligible for IC [42].…”

Section: Hypomethylating Agentsmentioning

confidence: 99%

Therapeutic Choice in Older Patients with Acute Myeloid Leukemia: A Matter of Fitness

Palmieri

Paterno

Bellis

et al. 2020

Cancers

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Acute myeloid leukemia (AML), with an incidence increasing with age, is the most common acute leukemia in adults. Concurrent comorbidities, mild to severe organ dysfunctions, and low performance status (PS) are frequently found in older patients at the onset, conditioning treatment choice and crucially influencing the outcome. Although anthracyclines plus cytarabine-based chemotherapy, also called “7 + 3” regimen, remains the standard of care in young adults, its use in patients older than 65 years should be reserved to selected cases because of higher incidence of toxicity. These adverse features of AML in the elderly underline the importance of a careful patient assessment at diagnosis as a critical tool in the decision-making process of treatment choice. In this review, we will describe selected recently approved drugs as well as examine prognostic algorithms that may be helpful to assign treatment in elderly patients properly.

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Hypomethylating Agents as a Therapy for AML

Cited by 51 publications

References 94 publications

Advances in targeted therapy for acute myeloid leukaemia

Advances in targeted therapy for acute myeloid leukaemia

Decitabine induces regulatory T cells, inhibits the production of IFN-gamma and IL-17 and exerts preventive and therapeutic efficacy in rodent experimental autoimmune neuritis

Therapeutic Choice in Older Patients with Acute Myeloid Leukemia: A Matter of Fitness

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