The development and clinical use of oral hypomethylating agents in acute myeloid leukemia and myelodysplastic syndromes: dawn of the total oral therapy era

References

• Montalban‐Bravo G. and Garcia‐Manero G. Myelodysplastic syndromes: 2018 update on diagnosis, risk‐stratification and management.. Am J Hematol. 2018;93(1):129–147
   Google Scholar
• Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–2405.
   PubMed Web of Science ®Google Scholar
• Bejar R, Papaemmanuil E, Haferlach T, et al. Somatic mutations in MDS patients are associated with clinical features and predict prognosis independent of the IPSS-R: analysis of combined datasets from the international working group for prognosis in MDS-molecular committee. Blood. 2015;126(23):907.
   Web of Science ®Google Scholar
• Steensma DP. How I use molecular genetic tests to evaluate patients who have or may have myelodysplastic syndromes. Blood. 2018;132(16):1657–1663.
   PubMed Web of Science ®Google Scholar
• Papaemmanuil E, Gerstung M, Malcovati L, et al. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood. 2013;122(22):3616–3627.
   PubMed Web of Science ®Google Scholar
• Klepin H, Rao A, Pardee T. Acute myeloid leukemia and myelodysplastic syndromes in older adults. J Clin Oncol. 2014;32(24):2541–2552.
   PubMed Web of Science ®Google Scholar
• Dohner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424–447.
   PubMed Web of Science ®Google Scholar
• Farag SS, Archer KJ, Mro´zek K, et al. Pretreatment cytogenetics add to other prognostic factors predicting complete remission and long-term outcome in patients 60 years of age or older with acute myeloid leukemia: results from Cancer and Leukemia Group B 8461. Blood. 2006;108(1):63–73.
   PubMed Web of Science ®Google Scholar
• Grimwade D, Walker H, Harrison G, et al. The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML): analysis of 1065 patients entered into the United Kingdom medical research council AML11 trial. Blood. 2001;98(5):1312–1320.
   PubMed Web of Science ®Google Scholar
• Patel BJ, Przychodzen B, Thota S, et al. Genomic determinants of chronic myelomonocytic leukemia. Leukemia. 2017;31(12):2815–2823.
   PubMed Web of Science ®Google Scholar
• Issa JP, Kantarjian H. Targeting DNA Methylation. Clin Cancer Res. 2009;15(12):3938–3946.
   Web of Science ®Google Scholar
• Sato T, Issa JP, Kropf P. DNA hypomethylating drugs in cancer therapy. Cold Spring Harb Perspect Med. 2017;7(5):a026948.
   PubMed Web of Science ®Google Scholar
• Zhang W, Xu J. DNA methyltransferases and their roles in tumorigenesis. Biomark Res. 2017;5(1):1.
   PubMedGoogle Scholar
• National Comprehensive Cancer Network. Myelodysplastic Syndromes (Version 3.2021). [cited 2021 Feb 1]. Avalaible from: https://www.nccn.org/professionals/physician_gls/pdf/mds.pdf
   Google Scholar
• Malcovati L, Hellström-Lindberg E, Bowen D et al. Diagnosis and treatment of primary myelodysplastic syndromes in adults: recommendations from the European LeukemiaNet. Blood. 2013;122(17):2943–2964
   PubMed Web of Science ®Google Scholar
• Prebet T, Charbonnier A, Gelsi-Boyer V, et al. Lenalidomide treatment for patients with myelodysplastic syndrome and low blast count acute myeloid leukemia after azacitidine failure. Leuk Lymphoma. 2013;54(7):1538–1540.
   PubMed Web of Science ®Google Scholar
• Fenaux P, Platzbecker U, Mufti GJ, et al. Luspatercept in patients with lower-risk myelodysplastic syndromes. N Engl J Med. 2020;382(2):140–151.
   PubMed Web of Science ®Google Scholar
• Bewersdorf JP. Carraway H and Prebet T. Emerging treatment options for patients with high-risk myelodysplastic syndrome. Ther Adv Hematol. 2020;11:1–22.
   Web of Science ®Google Scholar
• Xie M. Jiang Q and Xie Y. Comparison between decitabine and azacitidine for the treatment of myelodysplastic syndrome: a meta‐analysis with 1392 participants. Clin Lymphoma Myeloma Leuk. 2015;15(1):22–28.
   PubMed Web of Science ®Google Scholar
• Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase iii study. Lancet Oncol. 2009;10(3):223–232.
   PubMed Web of Science ®Google Scholar
• Kantarjian H, Issa JP, Rosenfeld CS, et al. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase iii randomized study. Cancer. 2006;106(8):1794–1803.
   PubMed Web of Science ®Google Scholar
• Lubbert M, Suciu S, Baila BH, et al. Low-dose decitabine versus best supportive care in elderly patients with intermediate- or high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy: final results of the randomized phase III study of the European organisation for research and treatment of cancer leukemia group and the German MDS study group. J Clin Oncol. 2011;29(15):1987–1996.
   PubMed Web of Science ®Google Scholar
• Silverman LR, Demakos EP, Peterson BL, et al. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group b. J Clin Oncol. 2002;20(10):2429–2440.
   PubMed Web of Science ®Google Scholar
• Santini V. How I treat MDS after hypoemthylating agent failure. Blood. 2019;133(6):521–529.
   PubMed Web of Science ®Google Scholar
• DeZern AE. Nine years without a new FDA-approved therapy for MDS: how can we break through the impasse? Hematology Am Soc Hematol Educ Program. 2015;1(1):308–316.
   Google Scholar
• National Comprehensive Cancer Network. (2020). Acute Myeloid Leukemia (version 2.2020). Retrieved from https://www.nccn.org/professionals/physician_gls/pdf/aml_blocks.pdf. Accessed 2020 Feb 1
   Google Scholar
• Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol. 2010;28(4):562–569.
   PubMed Web of Science ®Google Scholar
• Kantarjian HF, Thomas XG, Dmoszynska A, et al. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol. 2012;30(21):2670–2677.
   PubMed Web of Science ®Google Scholar
• Cashen AF, Schiller GJ, O’Donell MR, et al. Multicenter, phase II study of decitabine for the first-line treatment of older patients with acute myeloid leukemia. J Clin Oncol. 2010;28(4):556–561.
   PubMed Web of Science ®Google Scholar
• DiNardo CD, Jonas BA, Pullarkat MJ, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med. 2020;383(7):617–629.
   PubMed Web of Science ®Google Scholar
• Dombret H, Seymour JF, Butrym A, et al. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with .30% blasts. Blood. 2015;126(3):291–299.
   PubMed Web of Science ®Google Scholar
• DiNardo CD, Pratz K, Pullarkat V, et al. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019;133(1):7–17.
   PubMed Web of Science ®Google Scholar
• Onureg. Package insert. Celgene Corporation; 2020.
   Google Scholar
• Inqovi. Package insert. Otsuka Pharmaceutical Co.; 2020
   Google Scholar
• Vidaza, Package insert. Celgene Corporation; 2011.
   Google Scholar
• Dacogen. Package insert. Otsuka Pharmaceutical Co.,2020.
   Google Scholar
• US Food and Drug Administration. FDA approves new treatment for myelodysplastic syndrome (MDS) That Can Be Taken at Home. July 07, 2020. https://www.fda.gov/news-events/press-announcements/fda-approves-new-therapy-myelodysplastic-syndromes-mds-can-be-taken-home. Accessed 2020 Dec 19
   Google Scholar
• US Food and Drug Administration. FDA approves Onureg (azacitidine tablets) for acute myeloid leukemia. September 01, 2020. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-onureg-azacitidine-tablets-acute-myeloid-leukemia#:~:text=On%20September%201%2C%202020%2C%20the,recovery%20(CRi)%20following%20intensive%20induction Accessed 2020 Dec 19
   Google Scholar
• Garcia-Manero G, Griffiths EA, Steensma DP, et al., Oral cedazuridine/decitabine for MDS and CMML: a phase 2 pharmacokinetic/pharmacodynamic randomized crossover study. Blood. 2020;136(6): 674–683.
   PubMed Web of Science ®Google Scholar
• Garcia-Manero G, McCloskey J, Griffiths EA, et al. Pharmacokinetic exposure equivalence and preliminary efficacy and safety from a randomized cross over phase 3 study (ASCERTAIN study) of an oral hypomethylating agent ASTX727 (cedazuridine/decitabine) compared to iv decitabine [abstract]. 61st American Society of Hematology (ASH) Annual Meeting, Orlando, FL, US. 2019 Dec 10. Abstract #846
   Google Scholar
• Wei A, Dohner H, Pocock C, et al., Oral azacitidine maintenance therapy for acute myeloid leukemia in first remission. N Engl J Med. 2020;383(26): 2526–2537.
   PubMed Web of Science ®Google Scholar
• Stoltz ML, Etter JB, Obradovic T, et al. Development of an oral dosage form of azacitidine: overcoming challenges in chemistry, formulation, and bioavailability. Blood 2006;108(11):4850.
   Web of Science ®Google Scholar
• Mistry B, Jones MM, Kubiak P, et al. A Phase 1 study to assess the absolute bioavailability and safety of an oral solution of decitabine in subjects with myelodysplastic syndromes (MDS). Blood. 2011;118(21):3801.
   Web of Science ®Google Scholar
• Lavelle D, Vaitkus K, Ling Y, et al. Effects of tetrahydrouridine on pharmacokinetics and pharmacodynamics of oral decitabine. Blood. 2012;119(5):1240–1247.
   PubMed Web of Science ®Google Scholar
• Molokie R, Lavelle D, Gowhari M, et al. Oral tetrahydrouridine and decitabine for non-cytotoxic epigenetic gene regulation in sickle cell disease: a randomized phase 1 study. PLoS Med. 2017;14(9):e1002382.
   PubMed Web of Science ®Google Scholar
• Kelley JA, Driscoll JS, McCormack JJ, et al. Furanose-pyranose isomerization of reduced pyrimidine and cyclic urea ribosides. J Med Chem. 1986;29(11):2351–2358.
   PubMed Web of Science ®Google Scholar
• Ferraris D, Duvall B, Delahanty G, et al. Design, synthesis, and pharmacological evaluation of fluorinated tetrahydrouridine derivatives as inhibitors of cytidine deaminase. J Med Chem. 2014;57(6):2582–2588.
   PubMed Web of Science ®Google Scholar
• Savona MR, Odenike O, Amrein PC, et al. An oral fixed-dose combination of decitabine and cedazuridine in myelodysplastic syndromes: a multicentre, open-label, dose-escalation, phase 1 study. Lancet Haematol. 2019;6(4):e194–e203.
   PubMed Web of Science ®Google Scholar
• Oganesian A, Redkar S, Taverna P, et al. Preclinical data in cynomolgus (cyn) monkeys of ASTX727, a novel oral hypomethylating agent (HMA) composed of low-dose oral decitabine combined with a novel cytidine deaminase inhibitor (CDAi) E7727. Blood. 2013;122(21):2526.
   Web of Science ®Google Scholar
• Savona MR, McCloskey JK, Griffiths EA, et al. Clinical efficacy and safety of oral decitabine/cedazuridine in 133 patients with myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). [abstract]. 61st American Society of Hematology (ASH) Annual Meeting, Orlando, Florida, United States. Dec 2019. Abstract #1230
   Google Scholar
• Garcia-Manero G, Sd G, Cogle C, et al., Phase I study of oral azacitidine in myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia. J Clin Oncol. 2011;29(18): 2521–2527.
   PubMed Web of Science ®Google Scholar
• Ward MR, Stoltz ML, Etter JB, et al. An oral dosage formulation of azacitidine: a pilot pharmacokinetic study. J Clin Oncol. 2007;25(18_suppl):7084.
   Web of Science ®Google Scholar
• Garcia-Manero G, Stoltz ML, Ward MR, et al. A pilot pharmacokinetic study of oral azacitidine. Leukemia. 2008;22(9):1680–1684.
   PubMed Web of Science ®Google Scholar
• Gore S, Cogle CR, Skikne B, et al. Oral azacitidine (AZA) activity in patients with acute myelogenous leukemia (AML). Blood. 2011;118(21):1546.
   Web of Science ®Google Scholar
• Cogle CR, Scott BL, Boyd T, et al. Oral azacitidine (CC-486) for the treatment of myelodysplastic syndromes and acute myeloid leukemia. Oncologist. 2015;20(12):1404–1412.
   PubMed Web of Science ®Google Scholar
• Laille E, Shi T, Garcia-Manero G, et al. Pharmacokinetics and pharmacodynamics with extended dosing of CC-486 in patients with hematologic malignancies. PLoS ONE. 2015;10(8):e0135520.
   PubMed Web of Science ®Google Scholar
• Garcia-Manero G, Gore SD, Kambhampati S, et al. Efficacy and safety of extended dosing schedules of CC-486 (oral azacitidine) in patients with lower-risk myelodysplastic syndromes. Leukemia. 2016;30(4):889–896.
   PubMed Web of Science ®Google Scholar
• Garcia-Manero G, Gore SD, Cogle CR, et al. Evaluation of oral azacitidine using extended treatment schedules: a phase i study. Blood. 2010;116(21):603.
   PubMed Web of Science ®Google Scholar
• NDA Multi-disciplinary Review and Evaluation NDA 212576, Original INQOVI (decitabine and cedazuridine). https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212576Orig1s000MultidisciplineR.pdf. Accessed 2021 Feb 20
   Google Scholar
• Wei AH, Dohner H, Pocock C, et al. The QUAZAR AML-001 maintenance trial: results of a phase III international, randomized, double-blind, placebo-controlled study of CC-486 (oral formulation of azacitidine) in patients with acute myeloid leukemia (AML) in first remission. Blood. 2019;134(Supplement_2):LBA–3.
   Google Scholar
• Steensma DP, Baer MR, Slack JL, et al. Multicenter study of decitabine administered daily for 5 days every 4 weeks to adults with myelodysplastic syndromes: the alternative dosing for outpatient treatment (ADOPT) trial. J Clin Oncol. 2009;27(23):3842–3848.
   PubMed Web of Science ®Google Scholar
• Savona MR, Kolibaba K, Conkling P, et al. Extended dosing with CC-486 (oral azacitidine) in patients with myeloid malignancies. Am J Hematol. 2018;93(10):1199–1206.
   PubMed Web of Science ®Google Scholar
• Roboz GJ, Ravandi F, Wei A, et al. Oral azacitidine (CC-486) prolongs survival for patients with acute myeloid leukemia (AML) in remission after intensive chemotherapy (IC) independent of the presence of measurable residual disease (MRD) at study entry: results from the QUAZAR AML-001 trial [abstract]. 61st American Society of Hematology (ASH) Annual Meeting, Orlando, Florida, United States. Dec 2019. Abstract #692
   Google Scholar
• Roboz GJ, Döhner H, Pocock C et al. Health-related quality of life with oral azacitidine (oral AZA) in patients with acute myeloid leukemia (AML) in first remission following induction chemotherapy (IC): results from the phase III QUAZAR AML-001 trial [abstract]. 61st American Society of Hematology (ASH) Annual Meeting, Orlando, Florida, United States. Dec 2019. Abstract #214
   Google Scholar
• Wei A, Roboz GJ, Dombret H, et al. CC-486 improves overall survival (OS) and relapse-free survival (RFS) for patients with acute myeloid leukemia (AML) in first remission after intensive chemotherapy (IC), regardless of amount of consolidation received: results from the phase III QUAZAR AML-001 maintenance trial. Blood. 2020;136(Supplement 1):38–40.
   Google Scholar
• Roboz GJ, Ravandi F, Wei AH, et al. CC-486 prolongs survival for patients with acute myeloid leukemia (AML) in remission after intensive chemotherapy (IC) independent of the presence of measurable residual disease (MRD) at study entry: results from the QUAZAR AML-001 maintenance trial. Blood. 2020;136(Supplement 1):32–33.
   Google Scholar
• Musto P, Maurillo L, Spagnoli A, et al. Azacitidine for the treatment of lower risk myelodysplastic syndromes: a retrospective study of 74 patients enrolled in an Italian named patient program. Cancer. 2010;116(6):1485–1494.
   PubMed Web of Science ®Google Scholar
• Al Ameri A, Jabbour E, Garcia-Manero G, et al. Significance of thrombocytopenia in myelodysplastic syndromes: associations and prognostic implications. Clin. Lymphoma Myeloma Leuk. 2011;11(2):237–241.
   PubMed Web of Science ®Google Scholar
• Garcia-Manero G, Scott B, Cogle C, et al. CC-486 (oral azacitidine) in patients with myelodysplastic syndromes with pretreatment thrombocytopenia. Leuk Res. 2018;72:79–85.
   PubMed Web of Science ®Google Scholar
• Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study, Lancet Oncol. The Lancet. Oncology. 2009;10(3):223–232.
   PubMed Web of Science ®Google Scholar
• Garcia-Manero G, Almeida A, Giagounidis A, et al. Design and rationale of the QUAZAR lower-risk MDS (AZA-MDS-003) trial: a randomized phase 3 study of CC-486 (oral azacitidine) plus best supportive care vs placebo plus best supportive care in patients with IPSS lower-risk myelodysplastic syndromes and poor prognosis due to red blood cell transfusion–dependent anemia and thrombocytopenia. BMC Hematol. 2016;16:12.
   PubMedGoogle Scholar
• Garcia-Manero G, Santini V, Almeida A, et al. A phase III placebo-controlled trial of CC-486 in patients with red blood cell transfusion-dependent (RBC-TD) anemia and thrombocytopenia due to IPSS lower-risk myelodysplastic syndromes. [Abstract] 25th EHA Congress, Frankfurt, Germany. June 2020. Abstract S180
   Google Scholar
• Xu T, Kingsley L, DiNucci S, et al. Safety and utilization of peripherally inserted central catheters versus midline catheters at a large academic medical center. Am J Infect Control. 2016;44(12):1458–1461.
   PubMed Web of Science ®Google Scholar
• Ferruccio LF, Murray C, Yee KW, et al. Tolerability of Vidaza (azacitidine) subcutaneous administration using a maximum volume of 3 ml per injection. J Oncol Pharm Pract. 2016;22(4):605–610.
   PubMed Web of Science ®Google Scholar
• Welch JS, Petti AA, Miller CA, et al. TP53 and decitabine in acute myeloid leukemia and myelodysplastic Syndromes. Engl J Med. 2016;375(21):2023–2036.
   PubMed Web of Science ®Google Scholar
• Becker H, Pfeifer D, Ihorst G, et al. Monosomal karyotype and chromosome 17p loss or TP53 mutations in decitabine-treated patients with acute myeloid leukemia. Ann Hematol. 2020;99(7):1551–1560.
   PubMed Web of Science ®Google Scholar
• Middeke J, Teipel R, Röllig C et al. Decitabine treatment in 311 patients with acute myeloid leukemia: outcome and impact of TP53 mutations – a registry based analysis.
   Google Scholar
• Leukemia & Lymphoma;, ahead-of-print, 1–15 (2020)
   Google Scholar
• Sallman D. To target the untargetable: elucidation of synergy of APR-246 and azacitidine in TP53 mutant myelodysplastic syndromes and acute myeloid leukemia. Haematologica. 2020;105(6):1470–1472.
   PubMed Web of Science ®Google Scholar
• Roboz GJ, Montesinos P, Selleslag D, et al. Design of the randomized, phase III, QUAZAR AML maintenance trial of CC-486 (oral azacitidine) maintenance therapy in acute myeloid leukemia. Future Oncol. 2016;12(3):293–302.
   PubMed Web of Science ®Google Scholar
• Ye W, Gunti S, Allen CT, et al. ASTX660, an antagonist of cIAP1/2 and XIAP, increases antigen processing machinery and can enhance radiation-induced immunogenic cell death in preclinical models of head and neck cancer. OncoImmunology. 2020;9(1):1710398.
   PubMed Web of Science ®Google Scholar
• De Lima M, Oran B, Champlin R, et al. CC-486 maintenance after stem cell transplantation in patients with acute myeloid leukemia or myelodysplastic syndromes. Biol Blood Marrow Transplant. 2018;24(10):2017–2024.
   PubMed Web of Science ®Google Scholar
• Oran B, De Lima M, Garcia-Manero G, et al. A phase 3 randomized study of 5-azacitidine maintenance vs observation after transplant in high-risk AML and MDS patients. Blood Adv. 2020;4(21):5580–5588.
   PubMed Web of Science ®Google Scholar
• Bernal T, Martinez-Camblor P, Sanchez-Garcia J, et al. Effectiveness of azacitidine in unselected high-risk myelodysplastic syndromes: results from the Spanish registry. Leukemia. 2015;29(9):1875–1881.
   PubMed Web of Science ®Google Scholar
• Zeidan AM, Hu X, Zhu W, et al. Association of provider experience and clinical outcomes in patients with myelodysplastic syndromes receiving hypomethylating agents. Leuk Lymphoma. 2020;61(2):397–408.
   PubMed Web of Science ®Google Scholar
• Papaemmanuil E, Gerstung M, Bullinger L, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 2016;374(23):2209–2221.
   PubMed Web of Science ®Google Scholar
• Platzbecker U, Middeke JM, Sockel K, et al. Measurable residual disease-guided treatment with azacitidine to prevent haematological relapse in patients with myelodysplastic syndrome and acute myeloid leukaemia (RELAZA2): an open-label, multicentre, phase 2 trial. Lancet Oncol. 2018;19(12):1668–1679.
   PubMed Web of Science ®Google Scholar
• Gao L, Zhang Y, Wang S, et al. Effect of rhG-CSF combined with decitabine prophylaxis on relapse of patients with high-risk MRD-negative AML after HSCT: an open-label, multicenter, randomized controlled trial. J Clin Oncol. 2020;38(36):4249–4259.
   PubMed Web of Science ®Google Scholar
• Sallman DA, DeZern AE, Garcia-Manero G, et al. Eprenetapopt (APR-246) and azacitidine in TP53-mutant myelodysplastic syndromes. J Clin Oncol. 2021;0:JCO.20.02341.
   Google Scholar
• Sallman DA, Asch AS, Al Malki MM, et al. The first-in-class anti-CD47 antibody magrolimab (5F9) in combination with azacitidine is effective in MDS and AML patients: ongoing phase 1b results. Blood. 2019;134(Supplement_1):569.
   Web of Science ®Google Scholar
• Riether C, Pabst T, Höpner S, et al. Targeting CD70 with cusatuzumab eliminates acute myeloid leukemia stem cells in patients treated with hypomethylating agents. Nat Med. 2020;26(9):1459–1467.
   PubMed Web of Science ®Google Scholar
• Coiante S, Korbel G Aprea therapeutics announces results of primary endpoint from phase 3 trial of eprenetapopt in TP53 mutant myelodysplastic syndromes (MDS). Available from: https://ir.aprea.com/news-releases/news-release-details/aprea-therapeutics-announces-results-primary-endpoint-phase-3. Accessed 2021 Feb 28
   Google Scholar
• Buckland M Astex and otsuka announce results of phase 3 ASTRAL-2 and ASTRAL-3 studies of guadecitabine (SGI-110) in patients with previously treated acute myeloid leukemia (AML) and myelodysplastic syndromes or chronic myelomonocytic leukemia (MDS/CMML) 2020. Available from: https://www.businesswire.com/news/home/20201014005914/en/Astex-and-Otsuka-Announce-Results-of-Phase-3-ASTRAL-2-and-ASTRAL-3-Studies-of-Guadecitabine-SGI-110-in-Patients-with-Previously-Treated-Acute-Myeloid-Leukemia-AML-and-Myelodysplastic-Syndromes-or-Chronic-Myelomonocytic-Leukemia-MDSCMML. Accessed 2020 Dec 12
   Google Scholar
• Fenaux P, Gobbi M, Kropf P, et al. Results of ASTRAL-1, a phase 3 randomized trial of guadecitabine vs treatment choice (TC) in treatment-naïve acute myeloid leukemia not eligible for intensive chemotherapy. [Abstract] 25th EHA Congress, Amsterdam, Netherlands. June 2019 Abstract S879
   Google Scholar