Oral Azacitidine (CC-486) for the Treatment of Myeloid Malignancies

Döhner, Hartmut; Wei, Andrew H.; Torre, Ignazia La; Skikne, Barry S.; Beach, C.L.

doi:10.1016/j.clml.2021.09.021

Cited by 19 publications

(12 citation statements)

References 101 publications

(188 reference statements)

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“…CC-486 is an oral form of AZA, while ASTX727 is an oral decitabine analogue combined with cedazuridine -the cytidine deaminase inhibitor. They are characterized by other, more convenient methods of administration and give more comfort to the patient due to fewer visits and time at the hospital [36,41].…”

Section: Hypomethylating Drugsmentioning

confidence: 99%

Therapeutic options in high-risk myelodysplastic syndrome

Maksymowicz

Moqbil

Machowiec

et al. 2023

Hematology in Clinical Practice

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Myelodysplastic syndromes (MDS) constitute a heterogeneous group of diseases characterised by ineffective haematopoiesis, dysplasia and cytopenias. The treatment for high-risk MDS (HR-MDS) depends on individual factors such as the stage of the disease, age, comorbidities, and infections.Allogeneic haematopoietic stem cell transplantation (allo-HSCT) with reduced intensity conditioning has allowed more HR-MDS patients to be transplant-eligible, regardless of age. Hypomethylating agents, including azacitidine and decitabine, remain the standard of care for HR-MDS patients who are not qualified for curative allo-HSCT. Combination therapy of azacitidine with some new drugs resulted in higher response rates than azacitidine in monotherapy. Other targeted therapies are under investigation. They include HMA with different antibodies targeting immune checkpoints -programmed cell death (ligand) 1, cytotoxic T lymphocyte antigen 4, T-cell immunoglobulin mucin-3 or cluster of differentiation 47. Larger studies are necessary to confirm their efficacy in the treatment of HR-MDS.

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Section: Hypomethylating Drugsmentioning

confidence: 99%

Therapeutic options in high-risk myelodysplastic syndrome

Maksymowicz

Moqbil

Machowiec

et al. 2023

Hematology in Clinical Practice

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“…The oral formulation of azacitidine allows a prolonged schedule of administration, which consequently extends the exposure of AML cells to the drug, sparing inconveniences related to injections and promoting a particular hypomethylating profile and weaker cytotoxic effects [ 164 , 165 , 166 , 167 ].…”

Section: New Formulations Old Drugsmentioning

confidence: 99%

New Perspectives in Treating Acute Myeloid Leukemia: Driving towards a Patient-Tailored Strategy

Andreozzi

Massaro

Wittnebel

et al. 2022

IJMS

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For decades, intensive chemotherapy (IC) has been considered the best therapeutic option for treating acute myeloid leukemia (AML), with no curative option available for patients who are not eligible for IC or who have had failed IC. Over the last few years, several new drugs have enriched the therapeutic arsenal of AML treatment for both fit and unfit patients, raising new opportunities but also new challenges. These include the already approved venetoclax, the IDH1/2 inhibitors enasidenib and ivosidenib, gemtuzumab ozogamicin, the liposomal daunorubicin/cytarabine formulation CPX-351, and oral azacitidine. Venetoclax, an anti BCL2-inhibitor, in combination with hypomethylating agents (HMAs), has markedly improved the management of unfit and elderly patients from the perspective of improved quality of life and better survival. Venetoclax is currently under investigation in combination with other old and new drugs in early phase trials. Recently developed drugs with different mechanisms of action and new technologies that have already been investigated in other settings (BiTE and CAR-T cells) are currently being explored in AML, and ongoing trials should determine promising agents, more synergic combinations, and better treatment strategies. Access to new drugs and inclusion in clinical trials should be strongly encouraged to provide scientific evidence and to define the future standard of treatment in AML.

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“…A total of 236 patients were taken into consideration and were given 300 mg for 14 days to treat AML. The frequencies of thrombocytopenia, anemia, and neutropenia were 33%, 20%, and 44%, respectively [159]. The toxic effect of azacitidine was also evaluated in another cohort of MDS patients.…”

Section: Hematological Toxicities Of Anticancer Nucleoside Drugsmentioning

confidence: 99%

“…A total of 107 patients were taken into consideration: 300 mg/day was given to them for 21 days and the side effects were analyzed. Of these 107 patients, 20 were affected by anemia, 31 by thrombocytopenia, and 50 by neutropenia [159,160]. The frequency ranges of various hematological toxicities observed in various studies are shown in Table 2.…”

Section: Hematological Toxicities Of Anticancer Nucleoside Drugsmentioning

confidence: 99%

Solute Carrier Nucleoside Transporters in Hematopoiesis and Hematological Drug Toxicities: A Perspective

Ali

Raj

Kaur

et al. 2022

Cancers

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Anticancer nucleoside analogs produce adverse, and at times, dose-limiting hematological toxicities that can compromise treatment efficacy, yet the mechanisms of such toxicities are poorly understood. Recently, cellular nucleoside transport has been implicated in normal blood cell formation with studies from nucleoside transporter-deficient mice providing additional insights into the regulation of mammalian hematopoiesis. Furthermore, several idiopathic human genetic disorders have revealed nucleoside transport as an important component of mammalian hematopoiesis because mutations in individual nucleoside transporter genes are linked to various hematological abnormalities, including anemia. Here, we review recent developments in nucleoside transporters, including their transport characteristics, their role in the regulation of hematopoiesis, and their potential involvement in the occurrence of adverse hematological side effects due to nucleoside drug treatment. Furthermore, we discuss the putative mechanisms by which aberrant nucleoside transport may contribute to hematological abnormalities and identify the knowledge gaps where future research may positively impact treatment outcomes for patients undergoing various nucleoside analog therapies.

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Oral Azacitidine (CC-486) for the Treatment of Myeloid Malignancies

Abstract: and Amgen. AHW is a former employee of the Walter and Eliza Hall Institute and receives a fraction of its royalty stream related to venetoclax. ILT, BS, and CLB: Employment and equity interest: Bristol Myers Squibb.

Cited by 19 publications

References 101 publications

Therapeutic options in high-risk myelodysplastic syndrome

Therapeutic options in high-risk myelodysplastic syndrome

New Perspectives in Treating Acute Myeloid Leukemia: Driving towards a Patient-Tailored Strategy

Solute Carrier Nucleoside Transporters in Hematopoiesis and Hematological Drug Toxicities: A Perspective

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