Oral therapy for myelodysplastic syndromes/neoplasms and acute myeloid leukemia: a revolution in progress

References

• Cazzola M, Longo DL. Myelodysplastic syndromes. N Engl J Med. 2020;383(14):1358–1374. doi: 10.1056/NEJMra1904794
   PubMed Web of Science ®Google Scholar
• Short NJ, Rytting ME, Cortes JE. Acute myeloid leukaemia. Lancet. 2018;392(10147):593–606. doi: 10.1016/S0140-6736(18)31041-9
   PubMed Web of Science ®Google Scholar
• Sekeres MA, Taylor J. Diagnosis and treatment of myelodysplastic syndromes: a review. JAMA. 2022 Sep 6;328(9):872–880. doi: 10.1001/jama.2022.14578
   PubMed Web of Science ®Google Scholar
• Greenberg P, Cox C, LeBeau MM, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood J Am Soc Hematology. 1997;89(6):2079–2088. doi: 10.1182/blood.V89.6.2079
   Google Scholar
• Greenberg PL, Tuechler H, Schanz J, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood J Am Soc Hematology. 2012;120(12):2454–2465. doi: 10.1182/blood-2012-03-420489
   Google Scholar
• Bernard E, Tuechler H, Greenberg PL, et al. Molecular international prognostic scoring system for myelodysplastic syndromes. NEJM Evi. 2022;1(7):EVIDoa2200008. doi: 10.1056/EVIDoa2200008
   Google Scholar
• Carraway HE, Saygin C. Therapy for lower-risk MDS. Hematology Am Soc Hematol Educ Program. 2020 Dec 4;2020(1):426–433. doi: 10.1182/hematology.2020000127
   PubMedGoogle Scholar
• Fenaux P, Mufti G, Santini V, et al. Azacitidine (AZA) treatment prolongs overall survival (OS) in higher-risk MDS patients compared with conventional care regimens (CCR): results of the AZA-001 phase III study. Blood. 2007;110(11):817. doi: 10.1182/blood.V110.11.817.817
   Web of Science ®Google Scholar
• Kantarjian H, Issa JPJ, 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(8):1794–1803. doi: 10.1002/cncr.21792
   Google Scholar
• DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med. 2020;383(7):617–629. doi: 10.1056/NEJMoa2012971
   PubMed Web of Science ®Google Scholar
• Platzbecker U. Treatment of MDS. Blood. 2019 Mar 7;133(10):1096–1107. doi: 10.1182/blood-2018-10-844696
   PubMed Web of Science ®Google Scholar
• Wall SA, Devine S, Vasu S. The who, how and why: allogeneic transplant for acute myeloid leukemia in patients older than 60 years. Blood Rev. 2017;31(6):362–369. doi: 10.1016/j.blre.2017.07.002
   PubMed Web of Science ®Google Scholar
• Cannella L, Caocci G, Jacobs M, et al. Health-related quality of life and symptom assessment in randomized controlled trials of patients with leukemia and myelodysplastic syndromes: What have we learned? Crit Rev Oncol Hematol. 2015;96(3):542–554. doi: 10.1016/j.critrevonc.2015.07.012
   PubMed Web of Science ®Google Scholar
• Zeidan AM, Jayade S, Schmier J, et al. Injectable hypomethylating agents for management of myelodysplastic syndromes: patients’ perspectives on treatment. Clin Lymphoma Myeloma Leukemia. 2022;22(3):e185–e198. doi: 10.1016/j.clml.2021.09.009
   PubMed Web of Science ®Google Scholar
• Venugopal S, Mascarenhas J, Steensma DP. Loss of 5q in myeloid malignancies–A gain in understanding of biological and clinical consequences. Blood Rev. 2021;46:100735. doi: 10.1016/j.blre.2020.100735
   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(6):549–557. doi: 10.1056/NEJMoa041668
   PubMed Web of Science ®Google Scholar
• List A, Dewald G, Bennett J, et al. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med. 2006;355(14):1456–1465. doi: 10.1056/NEJMoa061292
   PubMed Web of Science ®Google Scholar
• Fenaux P, Giagounidis A, Selleslag D, et al. A randomized phase 3 study of lenalidomide versus placebo in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with del5q. Blood. 2011;118(14):3765–3776. doi: 10.1182/blood-2011-01-330126
   PubMed Web of Science ®Google Scholar
• Lopez-Cadenas F, Xicoy B, S RP, et al. Analysis of transfusion dependency development and disease evolution in patients with mds with 5q- and without transfusion needs at diagnosis. Blood. 2016;128(22):3180–3180. doi: 10.1182/blood.V128.22.3180.3180
   Web of Science ®Google Scholar
• López Cadenas F, Lumbreras E, González T, et al. Evaluation of lenalidomide (len) vs placebo in non-transfusion dependent low risk del(5q) MDS patients. final results of sintra-REV phase III international multicenter clinical trial. Blood. 2022;140(Supplement 1):1109–1111. doi: 10.1182/blood-2022-168718
   Google Scholar
• Sperling AS, Guerra VA, Kennedy JA, et al. Lenalidomide promotes the development of TP53-mutated therapy-related myeloid neoplasms. Blood. 2022 Oct 20;140(16):1753–1763. doi: 10.1182/blood.2021014956
   PubMed Web of Science ®Google Scholar
• Almeida A, Fenaux P, List AF, et al. Recent advances in the treatment of lower-risk non-del (5q) myelodysplastic syndromes (MDS). Leuk Res. 2017;52:50–57. doi:10.1016/j.leukres.2016.11.008
   PubMed Web of Science ®Google Scholar
• Santini V, Almeida A, Giagounidis A, et al. Randomized phase iii study of lenalidomide versus placebo in rbc transfusion-dependent patients with lower-risk non-del(5q) myelodysplastic syndromes and ineligible for or refractory to erythropoiesis-stimulating agents. J Clin Oncol. 2016;34(25):2988–2996. doi: 10.1200/JCO.2015.66.0118
   PubMed Web of Science ®Google Scholar
• Chen N, Hao C, Peng X, et al. Roxadustat for anemia in patients with kidney disease not receiving dialysis. N Engl J Med. 2019;381(11):1001–1010. doi: 10.1056/NEJMoa1813599
   PubMed Web of Science ®Google Scholar
• Dhillon S. Roxadustat: first global approval. Drugs. 2019;79(5):563–572. doi: 10.1007/s40265-019-01077-1
   PubMed Web of Science ®Google Scholar
• Henry DH, Glaspy J, Harrup R, et al. Roxadustat for the treatment of anemia in patients with lower‐risk myelodysplastic syndrome: open‐label, dose‐selection, lead‐in stage of a phase 3 study. American J Hematol. 2022;97(2):174–184. doi: 10.1002/ajh.26397
   PubMed Web of Science ®Google Scholar
• Gonzalez-Porras JR, Cordoba I, Such E, et al. Prognostic impact of severe thrombocytopenia in low-risk myelodysplastic syndrome. Cancer. 2011;117(24):5529–5537. doi: 10.1002/cncr.26173
   PubMed Web of Science ®Google Scholar
• Varghese LN, Defour JP, Pecquet C, et al. The thrombopoietin receptor: structural basis of traffic and activation by ligand, mutations, agonists, and mutated calreticulin. Front Endocrinol. 2017;8:59. doi:10.3389/fendo.2017.00059
   PubMed Web of Science ®Google Scholar
• Oliva EN, Alati C, Santini V, et al. Long term effects of eltrombopag treatment versus placebo for low-risk myelodysplastic syndromes with thrombocytopenia (EQoL-MDS): interim results of a single-blind, randomised, controlled, Phase 2 superiority trial. Blood. 2019;134(Supplement_1):3000. doi: 10.1182/blood-2019-126744
   Google Scholar
• Cheson BD, Greenberg PL, Bennett JM, et al. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood. 2006;108(2):419–425. doi: 10.1182/blood-2005-10-4149
   PubMed Web of Science ®Google Scholar
• Tamari R, Schinke C, Bhagat T, et al. Eltrombopag can overcome the anti-megakaryopoietic effects of lenalidomide without increasing proliferation of the malignant myelodysplastic syndrome/acute myelogenous leukemia clone. Leuk Lymphoma. 2014 Dec;55(12):2901–2906.
   PubMed Web of Science ®Google Scholar
• Gonzalez-Lugo JD, Kambhampati S, Yacoub A, et al. Lenalidomide and eltrombopag for treatment of low- or intermediate-risk myelodysplastic syndrome: result of a phase ii clinical trial. Clin Cancer Res. 2023 Jan 4;29(1):60–66. doi: 10.1158/1078-0432.CCR-22-1457
   PubMed Web of Science ®Google Scholar
• Garcia-Manero G, Gore S, 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. doi: 10.1038/leu.2015.265
   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. doi: 10.1371/journal.pone.0135520
   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 Hematology. 2016;16(1):1–9. doi: 10.1186/s12878-015-0037-1
   PubMedGoogle 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(13):1426. doi: 10.1200/JCO.20.02619
   PubMed Web of Science ®Google Scholar
• Kim N, Norsworthy KJ, Subramaniam S, et al. FDA approval summary: decitabine and cedazuridine tablets for myelodysplastic syndromes. Clin Cancer Res. 2022;OF1–OF6.
   Web of Science ®Google Scholar
• Patel AA, Cahill K, Saygin C, et al. Cedazuridine/Decitabine: from preclinical to clinical development in myeloid malignancies. Blood Adv. 2021;5(8):2264–2271. doi: 10.1182/bloodadvances.2020002929
   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. Blood. 2019;134(Supplement_1):846. doi: 10.1182/blood-2019-122980
   PubMed Web of Science ®Google Scholar
• Sasaki K, Jabbour E, Montalban-Bravo G, et al. Low-dose decitabine versus low-dose azacitidine in lower-risk MDS. NEJM Evi. 2022 2022 Sep 27;1(10):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(Supplement 1):1112–1114. doi: 10.1182/blood-2022-156512
   Google Scholar
• Bazinet A, Darbaniyan F, Jabbour E, et al. Azacitidine plus venetoclax in patients with high-risk myelodysplastic syndromes or chronic myelomonocytic leukaemia: phase 1 results of a single-centre, dose-escalation, dose-expansion, phase 1-2 study. Lancet Haematol. 2022 Oct;9(10):e756–e765.
   PubMed Web of Science ®Google Scholar
• Jabbour E, Garcia‐Manero G, Batty N, et al. Outcome of patients with myelodysplastic syndrome after failure of decitabine therapy. Cancer. 2010;116(16):3830–3834. doi: 10.1002/cncr.25247
   PubMed Web of Science ®Google Scholar
• Zeidan AM, Borate U, Pollyea DA, et al. A phase 1b study of venetoclax and azacitidine combination in patients with relapsed or refractory myelodysplastic syndromes. American J Hematol. 2023;98(2):272–281. doi: 10.1002/ajh.26771
   PubMed Web of Science ®Google Scholar
• Venugopal S, Kantarjian H, Maiti A, et al. A phase i/ii study of venetoclax in combination with ASTX727 (cedazuridine/decitabine) in treatment‐naïve high‐risk myelodysplastic syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML). Blood. 2021;138(Supplement 1):245. doi: 10.1182/blood-2021-153657
   Google Scholar
• Abuasab T, Garcia-Manero G, Short N, et al. Phase 2 Study of ASTX727 (cedazuridine/decitabine) plus venetoclax in patients with relapsed/refractory Acute Myeloid Leukemia (AML) or Previously Untreated, Elderly Patients with AML unfit for chemotherapy. Blood. 2022;140(Supplement 1):3324–3326. doi: 10.1182/blood-2022-158566
   Google Scholar
• Pulte ED, Norsworthy KJ, Wang Y, et al. FDA approval summary: gilteritinib for relapsed or refractory acute myeloid leukemia with a FLT3 MutationFDA Approval Summary: Gilteritinib. Clin Cancer Res. 2021;27(13):3515–3521. doi: 10.1158/1078-0432.CCR-20-4271
   PubMed Web of Science ®Google Scholar
• Perl AE, Martinelli G, Cortes JE, et al. Gilteritinib or chemotherapy for relapsed or refractory FLT3-Mutated AML. N Engl J Med. 2019;381(18):1728–1740. doi: 10.1056/NEJMoa1902688
   PubMed Web of Science ®Google Scholar
• Perl AE, Hosono N, Montesinos P, et al. Clinical outcomes in patients with relapsed/refractory FLT3-mutated acute myeloid leukemia treated with gilteritinib who received prior midostaurin or sorafenib. Blood Cancer J. 2022;12(5):1–9. doi: 10.1038/s41408-022-00677-7
   PubMed Web of Science ®Google Scholar
• Yilmaz M, Alfayez M, DiNardo CD, et al. Outcomes with sequential FLT3-inhibitor-based therapies in patients with AML. J Hematol Oncol. 2020 Oct 8;13(1):132.
   PubMed Web of Science ®Google Scholar
• Saxena K, Carter BZ, Konopleva M. EXABS-147-AML how do we overcome resistance to venetoclax. clinical lymphoma myeloma and leukemia. Clin Lymphoma Myeloma Leukemia. 2022;22:S55–S57. doi: 10.1016/S2152-2650(22)00660-7
   Web of Science ®Google Scholar
• Daver N, Perl AE, Maly J, et al. Venetoclax plus gilteritinib for FLT3-mutated relapsed/refractory acute Myeloid Leukemia. J Clin Oncol. 2022;40(35):4048–4059. doi: 10.1200/JCO.22.00602
   PubMed Web of Science ®Google Scholar
• Stein EM, DiNardo CD, Pollyea DA, et al. Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia. Blood. 2017 Aug 10;130(6):722–731.
   PubMed Web of Science ®Google Scholar
• de Botton, S, Montesinos P, Schuh AC, et al. Enasidenib vs conventional care in older patients with late-stage mutant-IDH2 relapsed/refractory AML: a randomized phase 3 trial. Blood. 2023 Jan 12;141(2):156–167.
   PubMed Web of Science ®Google Scholar
• DiNardo CD, Stein EM, de Botton S, et al. Durable remissions with ivosidenib in IDH1-mutated relapsed or refractory AML. N Engl J Med. 2018;378(25):2386–2398. doi: 10.1056/NEJMoa1716984
   PubMed Web of Science ®Google Scholar
• Atluri H, Maiti A, Sasaki K, et al. Phase ib/2 study of oral decitabine/cedazuridine (ASTX727) and venetoclax in combination with the targeted mutant IDH1 inhibitor ivosidenib or the targeted mutant IDH2 inhibitor enasidenib in IDH Mutated Acute Myeloid Leukemia. Blood. 2022;140(Supplement 1):6170–6172. doi: 10.1182/blood-2022-164986
   Google Scholar
• Watts JM, Baer MR, Yang J, et al. Olutasidenib alone or with azacitidine in IDH1-mutated acute myeloid leukaemia and myelodysplastic syndrome: phase 1 results of a phase 1/2 trial. Lancet Haematol. 2023 Jan;10(1):e46–e58.
   PubMed Web of Science ®Google Scholar
• de Botton, S, Fenaux P, Yee KWL, et al. Olutasidenib (FT-2102) induces durable complete remissions in patients with relapsed or refractory IDH1-mutated AML. Blood Adv. 2023 Feb 1;7(13):3117–3127.
   PubMed Web of Science ®Google Scholar
• Medeiros B, Fathi A, DiNardo C, et al. Isocitrate dehydrogenase mutations in myeloid malignancies. Leukemia. 2017;31(2):272–281. doi: 10.1038/leu.2016.275
   PubMed Web of Science ®Google Scholar
• DiNardo CD, Jabbour E, Ravandi F, et al. IDH1 and IDH2 mutations in myelodysplastic syndromes and role in disease progression. Leukemia. 2016;30(4):980–984. doi: 10.1038/leu.2015.211
   PubMed Web of Science ®Google Scholar
• DiNardo CD, Venugopal S, Lachowiez C, et al. Targeted therapy with the mutant IDH2 inhibitor enasidenib for high-risk IDH2-mutant myelodysplastic syndrome. Blood Adv. 2022;7(11):2378–2387. doi: 10.1182/bloodadvances.2022008378
   Web of Science ®Google Scholar
• Sebert M, Cluzeau T, Rauzy OB, et al. Ivosidenib monotherapy is effective in patients with IDH1 Mutated Myelodysplastic Syndrome (MDS): the idiome phase 2 study by the GFM group. Blood. 2021;138(Supplement 1):62. doi: 10.1182/blood-2021-146932
   Google Scholar
• Sallman DA, Foran JM, Watts JM, et al. Ivosidenib in patients with IDH1-mutant relapsed/refractory myelodysplastic syndrome (R/R MDS): updated enrollment and results of aphase 1 dose-escalation and expansion substudy J Clinic Onco. 2022;40(16_suppl): 7053–7053 .
   Web of Science ®Google Scholar
• Wei AH, Döhner H, Pocock C, et al. Oral azacitidine maintenance therapy for acute myeloid leukemia in first remission. N Engl J Med. 2020 Dec 24;383(26):2526–2537.
   PubMed Web of Science ®Google Scholar
• Ravandi F, Roboz GJ, Wei AH, et al. Management of adverse events in patients with acute myeloid leukemia in remission receiving oral azacitidine: experience from the phase 3 randomized QUAZAR AML-001 trial. J Hematol Oncol. 2021 Aug 28;14(1):133.
   PubMed Web of Science ®Google Scholar
• Jen EY, Wang X, Li M, et al. FDA approval summary: oral azacitidine for continued treatment of adults with acute myeloid leukemia unable to complete intensive curative therapy. Clin Cancer Res. 2022;28(14):OF1–OF5. doi: 10.1158/1078-0432.CCR-21-4525
   Web of Science ®Google Scholar