Efficacy of 10-day decitabine in acute myeloid leukemia

Bouligny, Ian Michael; Mehta, Vivek; Isom, S. Clay; Ellis, Leslie R.; Bhave, Rupali; Howard, Dianna S.; Lyerly, Susan; Manuel, Megan; Dralle, Sarah; Powell, Bayard L.; Pardee, Timothy S.

doi:10.1016/j.leukres.2021.106524

Cited by 7 publications

(3 citation statements)

References 36 publications

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“…Decitabine has been studied in AML at various doses and schedules. 12,39 Blum et al 40 have reported a CR rate of 47%, of which 64% achieved a morphologic leukemia-free state with a decitabine dose of 20 mg/m 2 administered for 10 consecutive days. Short et al 23 have reported that the response rate with a 5-day decitabine regimen was 44%, whereas that with a 10-day schedule of decitabine was 40%.…”

Section: Discussionmentioning

confidence: 99%

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Low-dose decitabine for previously untreated acute myeloid leukemia ineligible for intensive chemotherapy aged 65 years or older: a prospective study based on comprehensive geriatric assessment

Feng,

Zhang,

et al. 2023

Therapeutic Advances in Hematology

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Background: The outcome of patients with acute myeloid leukemia (AML) aged ⩾65 years is poor. Effective treatment options are limited for patients with AML who cannot tolerate intensive chemotherapy. Objectives: We aimed to evaluate the efficacy of low-dose decitabine in previously untreated patients with AML aged ⩾65 years who were ineligible for intensive chemotherapy based on a comprehensive geriatric assessment. Design: We performed a prospective, multicenter, open-label, and non-randomized study. Methods: Patients were enrolled at four centers in Beijing between 1 January 2017 and 31 December 2020. They were treated with decitabine at a dose of 6 mg/m2 for 10 days. The treatment was repeated every 28 days for one cycle for a total of six cycles. The primary endpoint of our study was overall survival (OS) at the end of the first year after enrolment. The secondary endpoints included overall response rate, leukemia-free survival, relapse rate, treatment-related mortality (TRM), quality of life, safety, and transfusion dependence. Patients were continuously monitored for toxicity. Results: Overall, 47 patients (30 males and 17 females) participated in this study. The median age of the enrolled patients was 78 (range, 65−90) years. The median follow-up time was 22.2 (range, 4.6−38.8) months. Fifteen (31.9%) patients achieved complete remission (CR), 11 (23.4%) patients achieved partial remission, 3 (6.4%) patients achieved hematological improvement only, and 18 (38.3%) patients did not achieve remission. The median time to obtain CR was 2 months. The median CR was 8.5 months. Of the patients, 36 (76.6%) patients completed six cycles of treatment with low-dose decitabine, and the 1-year OS was 36.1%. According to instrumental activities of daily living scales, age, comorbidities, and albumin (IACA) scores, the median survival was 11.2 months in the unfit group and 6 months in the frail group. The 1-year OS rates in the unfit and frail groups were 49.2% and 23.4%, respectively. Grade ⩾3 non-hematological toxicity was observed in 70.2% (33/47) of the patients. TRM occurred in three patients. No early deaths occurred after treatment. Conclusion: In newly diagnosed older patients with AML whose IACA assessment was unfit or frail for standard chemotherapy, treatment with low-dose decitabine demonstrated clinical activity and good security in our study.

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Section: Discussionmentioning

confidence: 99%

“…Decitabine has been studied in AML at various doses and schedules. 12 , 39 Blum et al. 40 have reported a CR rate of 47%, of which 64% achieved a morphologic leukemia-free state with a decitabine dose of 20 mg/m 2 administered for 10 consecutive days.…”

Section: Discussionmentioning

confidence: 99%

Low-dose decitabine for previously untreated acute myeloid leukemia ineligible for intensive chemotherapy aged 65 years or older: a prospective study based on comprehensive geriatric assessment

Feng,

Zhang,

et al. 2023

Therapeutic Advances in Hematology

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“…Intensity strategies offer a survival benefit in this population. Low-dose cytarabine or hypomethylating agents, such as azacitidine or decitabine, remain a mainstay of lower-intensity treatment with a median survival of 5 -9 months, varying by cytogenetic and molecular risk factors [4][5][6]. There is a persistent interest in intensifying lower-intensity treatment strategies to improve survival in the elderly population.…”

Section: Introductionmentioning

confidence: 99%

Augmenting Venetoclax Activity Through Signal Transduction in AML

Bouligny

Maher

Grant

2023

Journal of Cellular Signaling

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Venetoclax, a small-molecule B-cell lymphoma 2 (BCL-2) inhibitor, selectively eradicates leukemic stem cells (LSCs). While venetoclax has revolutionized the treatment of acute myeloid leukemia (AML), treatment failure and disease relapse are common. Mechanisms underlying venetoclax resistance are surprisingly heterogeneous. Venetoclax resistance encompasses a spectrum of genetic and epigenetic changes, with numerous pathways contributing to the upregulation of additional anti-apoptotic proteins. In this review, we address the mechanisms of venetoclax resistance in the context of signal transduction. We emphasize how aberrant cell signaling impairs apoptosis and predisposes to venetoclax failure. Commonly activated pathways, such as FLT3, PI3K/AKT/mTOR, and RAS, contribute to upregulated anti-apoptotic mediators and are frequently responsible for refractory disease or disease relapse. We highlight novel combination strategies aimed at disabling constitutively active signal transduction to augment response and overcome venetoclax resistance.

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Acute Myeloid Leukemia in Adults: Mast Cell Leukemia and Other Mast Cell Neoplasms

Stone¹,

Schiffer²,

DeAngelo³

2022

Holland‐Frei Cancer Medicine

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Overview Acute myeloid leukemia (AML) is a heterogeneous disease characterized by unbridled proliferation of myeloid stem cells resulting in bone marrow failure and death without effective therapy. The median age of AML is approximately 70; predisposing factors include inherited mutations, exposure to industrial solvents, ionizing radiation, or certain chemotherapy given for other malignancies or conditions. The disease results from the accumulation of mutations in pathways that promote cellular proliferation or impairing differentiation. Prognosis is based on a combination of host and disease factors, especially diagnostic cytogenetics and genomics. In younger fit patients, therapy consists of myelosuppressive induction chemotherapy to minimize disease burden and allow restoration of normal hematopoiesis. Postremission chemotherapy with additional myelo‐intense chemotherapy and/or allogeneic stem cell transplant is required to potentiate cure. In older and less fit patients (perhaps those with adverse prognosis) the current standard is repetitive cycles of a hypomethylating agent or low‐dose cytarabine plus the BCL‐2 inhibitor, venetoclax. The application of molecularly targeted therapies at both diagnosis and relapse may change the natural history of the disease, the management of which requires a comprehensive integration of disparate fields including social work, nutrition, pharmacy, blood bank, and medical oncology.

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Efficacy of 10-day decitabine in acute myeloid leukemia

Cited by 7 publications

References 36 publications

Low-dose decitabine for previously untreated acute myeloid leukemia ineligible for intensive chemotherapy aged 65 years or older: a prospective study based on comprehensive geriatric assessment

Low-dose decitabine for previously untreated acute myeloid leukemia ineligible for intensive chemotherapy aged 65 years or older: a prospective study based on comprehensive geriatric assessment

Augmenting Venetoclax Activity Through Signal Transduction in AML

Acute Myeloid Leukemia in Adults: Mast Cell Leukemia and Other Mast Cell Neoplasms

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