What value do cell cycle inhibitors have in the treatment of myelodysplastic syndrome?

References

• Tefferi A, Vardiman JW. Myelodysplastic syndromes. N Engl J Med. 2009;361:1872–1885. DOI:10.1056/NEJMra0902908
   PubMed Web of Science ®Google Scholar
• Esteller M. Epigenetics in cancer. N Engl J Med. 2008;358:1148–1159.
   PubMed Web of Science ®Google Scholar
• Reik W. Stability and flexibility of epigenetic gene regulation in mammalian development. Nature. 2007;447:425–432.
   PubMed Web of Science ®Google Scholar
• Yang X, Lay F, Han H, et al. Targeting DNA methylation for epigenetic therapy. Trends Pharmacol Sci. 2010;31:536–546.
   PubMed Web of Science ®Google Scholar
• Issa JP. DNA methylation as a therapeutic target in cancer. Clin Cancer Res. 2007;13:1634–1637. DOI:10.1158/1078-0432.CCR-06-2076
   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;20:2429–2440. DOI:10.1200/JCO.2002.04.117
   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;10:223–232. DOI:10.1016/S1470-2045(09)70003-8
   PubMed Web of Science ®Google Scholar
• Kantarjian H, Issa JJ, Rosenfeld CS, et al. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer: Interdiscip Int J Am Cancer Soc. 2006;106:1794–1803.
   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;136:674–683. DOI:10.1182/blood.2019004143
   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;93:1199–1206. DOI:10.1002/ajh.25216
   PubMed Web of Science ®Google Scholar
• Jabbour E, Short NJ, Montalban-Bravo G, et al. Randomized phase 2 study of low-dose decitabine vs low-dose azacitidine in lower-risk MDS and MDS/MPN. Blood. 2017;130:1514–1522. DOI:10.1182/blood-2017-06-788497
   PubMed Web of Science ®Google Scholar
• Koji S, Elias J, Guillermo M-B, et al. Low-dose decitabine versus low-dose azacitidine in lower-risk MDS. NEJM Evi. 2022;1:EVIDoa2200034. DOI:10.1056/EVIDoa2200034
   Google Scholar
• Garcia-Manero G, Bachiashvili K, Amin H, et al. ASTX727-03: phase 1 study evaluating oral decitabine/cedazuridine (ASTX727) Low-Dose (LD) in Lower-Risk Myelodysplastic Syndromes (LR-MDS) Patients. Blood. 2022;140:1112–1114. DOI:10.1182/blood-2022-156512
   Google Scholar
• Garcia-Manero G, Santini V, Almeida A, et al. Phase III, randomized, placebo-controlled trial of CC-486 (Oral Azacitidine) in patients with lower-risk myelodysplastic syndromes. J Clin Oncol. 2021;39:1426–1436. DOI:10.1200/JCO.20.02619
   PubMed Web of Science ®Google Scholar
• Kotla V, Goel S, Nischal S, et al. Mechanism of action of lenalidomide in hematological malignancies. J Hematol Oncol. 2009;2:1–10.
   PubMedGoogle Scholar
• Stahl M, Zeidan AM. Lenalidomide use in myelodysplastic syndromes: insights into the biologic mechanisms and clinical applications. Cancer. 2017;123:1703–1713. DOI:10.1002/cncr.30585
   PubMed Web of Science ®Google Scholar
• Wei S, Chen X, Rocha K, et al. A critical role for phosphatase haplodeficiency in the selective suppression of deletion 5q MDS by lenalidomide. Proc Natl Acad Sci. 2009;106:12974–12979. DOI:10.1073/pnas.0811267106
   PubMed Web of Science ®Google Scholar
• Fang J, Liu X, Bolanos L, et al. A calcium- and calpain-dependent pathway determines the response to lenalidomide in myelodysplastic syndromes. Nat Med. 2016;22:727–734. DOI:10.1038/nm.4127
   PubMed Web of Science ®Google Scholar
• List A, Kurtin S, Roe DJ, et al. Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med. 2005;352:549–557. DOI:10.1056/NEJMoa041668
   PubMed Web of Science ®Google Scholar
• Ball B, Komrokji RS, Adès L, et al. Evaluation of induction chemotherapies after hypomethylating agent failure in myelodysplastic syndromes and acute myeloid leukemia. Blood Adv. 2018;2:2063–2071. DOI:10.1182/bloodadvances.2018015529
   PubMed Web of Science ®Google Scholar
• Jabbour E, Faderl S, Sasaki K, et al. Phase 2 study of low-dose clofarabine plus cytarabine for patients with higher-risk myelodysplastic syndrome who have relapsed or are refractory to hypomethylating agents. Cancer. 2017;123:629–637. DOI:10.1002/cncr.30383
   PubMed Web of Science ®Google Scholar
• Montalban-Bravo G, Jabbour EJ, Estrov ZE, et al. Updated results of a phase 1/2 study of lower dose CPX-351 for patients with int-2 or high risk IPSS myelodysplastic syndromes and chronic myelomonocytic leukemia after failure to hypomethylating agents. Blood. 2021;138:3674. DOI:10.1182/blood-2021-151493
   Google Scholar
• Peterlin P, Turlure P, Chevallier P, et al. CPX 351 as first line treatment in higher risk MDS. a phase II trial by the GFM. Blood. 2021;138:243. DOI:10.1182/blood-2021-145123
   Google Scholar
• Reville PK, Kantarjian H, Borthakur G, et al. Venetoclax Combined with Cladribine, Idarubicin, Cytarabine (CLIA) as induction therapy in patients with newly diagnosed acute myeloid leukemia and high-risk myelodysplastic syndrome. Blood 2022;140:1702–1704. DOI:10.1182/blood-2022-167931
   PubMedGoogle Scholar
• De Botton S, Cluzeau T, Vigil CE, et al. SY-1425, a potent and selective RARα agonist, in combination with azacitidine demonstrates a high complete response rate and a rapid onset of response in RARA-Positive newly diagnosed unfit acute myeloid leukemia. Blood. 2020;136:4–5. DOI:10.1182/blood-2020-134600
   PubMedGoogle Scholar
• Dezern AE, Marconi G, Deeren D, et al. A randomized, double-blind, placebo-controlled study of tamibarotene/azacitidine versus placebo/azacitidine in newly diagnosed adult patients selected for RARA+ HR-MDS (SELECT-MDS-1). J Clin Oncol. 2022;40:TPS7075. DOI:10.1200/JCO.2022.40.16_suppl.TPS7075
   Google Scholar
• Agrawal V, Croslin C, Beltran AL, et al. Promising safety and efficacy results from an ongoing phase 1b study of pembrolizumab combined with decitabine in patients with relapsed/refractory (R/R) Acute Myeloid Leukemia (AML). Blood. 2022;140:6235–6236. DOI:10.1182/blood-2022-165894
   Google Scholar
• Zeidan AM, Ando K, Rauzy O, et al. Primary results of stimulus-MDS1: a randomized, double-blind, placebo-controlled phase II study of TIM-3 Inhibition with Sabatolimab Added to Hypomethylating Agents (HMAs) in adult patients with higher-risk Myelodysplastic Syndromes (MDS). Blood. 2022;140:2063–2065. DOI:10.1182/blood-2022-158612
   PubMedGoogle Scholar
• Savona MR, McCloskey JK, Griffiths EA, et al. Prolonged survival in bi-allelic TP53-mutated (Tp53mut) MDS subjects treated with oral decitabine/cedazuridine in the ascertain trial (ASTX727-02). Blood. 2022;140:2066–2069. DOI:10.1182/blood-2022-163841
   Google Scholar
• Zeidan AM, Mosher K, Souza S, et al. Phase 2 study of oral decitabine/cedazuridine in combination with magrolimab for previously untreated subjects with intermediate to very high-risk Myelodysplastic Syndromes (MDS). Blood. 2022;140:9779–9780. DOI:10.1182/blood-2022-158276
   Google Scholar
• Jonas BA, Yee K, Koller PB, et al. Preliminary results from a phase 2 open-label, multicenter, dose optimization clinical study of the safety, tolerability, and Pharmacokinetic (PK) and Pharmacodynamic (PD) profiles of Cfi-400945 as a single agent or in combination with azacitidine or decitabine in patients with acute myeloid leukemia, myelodysplastic syndrome or chronic myelomonocytic leukemia (TWT-202). Blood. 2022;140:9076–9077. DOI:10.1182/blood-2022-158370
   Google Scholar
• Riabov V, Xu Q, Schmitt N, et al. ASXL1 mutations are associated with a response to the combination of alvocidib and 5-azacytidine in higher-risk myelodysplastic syndromes. Blood. 2022;140:9749–9750. DOI:10.1182/blood-2022-165298
   Google Scholar
• Baeten JT, Agashe S, Quinet A, et al. Targeting ATR in TP53-mutant AML/MDS. Blood. 2022;140:8787–8788. DOI:10.1182/blood-2022-170238
   Google Scholar