561
Views
38
CrossRef citations to date
0
Altmetric
Drug Evaluation

Guadecitabine (SGI-110): an investigational drug for the treatment of myelodysplastic syndrome and acute myeloid leukemia

, &
Pages 835-849 | Received 04 Feb 2019, Accepted 10 Sep 2019, Published online: 19 Sep 2019

References

  • Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68:7–30.
  • Wiese M, Daver N. Unmet clinical needs and economic burden of disease in the treatment landscape of acute myeloid leukemia. Am J Manag Care. 2018;24:S347–S355.
  • Noone AM, Howlader N, Krapcho M, et al. SEER cancer statistics review, 1975-2015. Bethesda (MD): National Cancer Institute; 2018. Available from: https://seer.cancer.gov/csr/1975_2015/. Based on November 2017 SEER data submission, posted to the SEER web site, April 2018.
  • Cogle CR, Craig BM, Rollison DE, et al. Incidence of the myelodysplastic syndromes using a novel claims-based algorithm: high number of uncaptured cases by cancer registries. Blood. 2011;117:7121–7125.
  • Rollison DE, Howlader N, Smith MT, et al. Epidemiology of myelodysplastic syndromes and chronic myeloproliferative disorders in the United States, 2001-2004, using data from the NAACCR and SEER programs. Blood. 2008;112:45–52.
  • Rao AV. Fitness in the elderly: how to make decisions regarding acute myeloid leukemia induction. Hematology Am Soc Hematol Educ Program. 2016;2016:339–347.
  • Saber W, Horowitz MM. Transplantation for myelodysplastic syndromes: who, when, and which conditioning regimens. Hematology Am Soc Hematol Educ Program. 2016;2016:478–484.
  • Bell JA, Galaznik A, Huelin R, et al. Systematic literature review of treatment options and clinical outcomes for patients with higher-risk Myelodysplastic syndromes and chronic myelomonocytic leukemia. Clin Lymphoma Myeloma Leuk. 2018;18:e157–e166.
  • 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.
  • Kornblith AB, Herndon JE 2nd, Silverman LR, et al. Impact of azacytidine on the quality of life of patients with myelodysplastic syndrome treated in a randomized phase III trial: a Cancer and Leukemia Group B study. J Clin Oncol. 2002;20:2441–2452.
  • 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.
  • Kaminskas E, Farrell A, Abraham S, et al. Approval summary: azacitidine for treatment of myelodysplastic syndrome subtypes. Clin Cancer Res. 2005;11:3604–3608.
  • Kantarjian H, Issa JP, Rosenfeld CS, et al. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer. 2006;106:1794–1803.
  • Health Canada issues Notice of Compliance (NOC) for decitabine for the treatment of adult patients with de novo or secondary Myelodysplastic Syndrome (MDS), untreated or previously treated with chemotherapy, who are not considered candidates for hematopoietic stem cell transplantation. [cited 2019 Jul 28] Available from: https://www.canada.ca/en/health-canada/services/drug-health-product-review-approval/submissions-under-review.html
  • Dacogen [Summary of product characteristics]. London (UK): European Medicines Agency; 2013. [cited 2014 Jan 28]. Available from: [http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002221/human_med_001589.jsp&mid=WC0b01ac058001d124]
  • Kantarjian HM, 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;30:2670–2677.
  • Jabbour E, Garcia-Manero G, Batty N, et al. Outcome of patients with myelodysplastic syndrome after failure of decitabine therapy. Cancer. 2010;116:3830–3834.
  • Prebet T, Gore SD, Esterni B, et al. Outcome of high-risk myelodysplastic syndrome after azacitidine treatment failure. J Clin Oncol. 2011;29:3322–3327.
  • Medeiros BC, Fathi AT, DiNardo CD, et al. Isocitrate dehydrogenase mutations in myeloid malignancies. Leukemia. 2017;31:272–281.
  • Levis M. FLT3 mutations in acute myeloid leukemia: what is the best approach in 2013? Hematology Am Soc Hematol Educ Program. 2013;2013:220–226.
  • Cancer Genome Atlas Research N, Ley JT, Miller C, et al. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 2013;368:2059–2074.
  • Papaemmanuil E, Gerstung M, Bullinger L, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 2016;374:2209–2221.
  • Norsworthy KJ, Luo L, Hsu V, et al. FDA approval summary: ivosidenib for relapsed or refractory acute myeloid leukemia with an isocitrate dehydrogenase-1 mutation. Clin Cancer Res. 2019;25:3205–3209.
  • Stein EM, DiNardo CD, Pollyea DA, et al. Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia. Blood. 2017;130:722–731.
  • FDA granted regular approval to enasidenib for the treatment of relapsed or refractory AML. Silver Spring (MD): U.S Food & Drug Administration. [cited 2019 Jan 25] Available from: https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm569482.htm
  • 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;378:2386–2398.
  • FDA approves gilteritinib for relapsed or refractory acute myeloid leukemia (AML) with a FLT3 mutation. U.S Food & Drug. Silver Spring, MD. Administration. [cited 2019 Jan 25] Available from: https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm627045.htm.
  • Perl AE, Martinelli G, Cortes JE et al. Gilteritinib significantly prolongs overall survival in patients with FLT3-mutated (FLT3mut+) relapsed/refractory (R/R) acute myeloid leukemia (AML): results from the Phase III ADMIRAL trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA.Philadelphia (PA): AACR. Cancer Research 2019. p. 79. Abstract nr CT184.
  • 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;133:7–17.
  • FDA approves venetoclax in combination for AML in adults. Silver Spring (MD): U.S Food & Drug Administration. [cited 2019 Jan 25]. Available from:https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm626499.htm
  • Cortes JE, Heidel FH, Hellmann A, et al. Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. Leukemia. 2018;33(2):379–389.
  • FDA approves glasdegib for AML in adults age 75 or older or who have comorbidities. Silver Spring (MD): U.S Food & Drug Administration. [cited 2019 Jan 25]. Available from: https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm626494.htm
  • Roboz GJ, DiNardo CD, Stein EM, et al. Ivosidenib (AG-120) induced durable remissions and transfusion independence in patients with IDH1-mutant untreated AML: results from a phase 1 dose escalation and expansion study. Blood. 2018;132:561.
  • FDA approves ivosidenib as first-line treatment for AML with IDH1 mutation. [cited 2019 Jul 29]. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-ivosidenib-first-line-treatment-aml-idh1-mutation
  • Health Canada issues notice of compliance with conditions (NOC/c) for IDHIFA™ the first oral targeted therapy for adult patients with relapsed or refractory acute myeloid leukemia and an IDH2 mutation. [cited 2019 Jul 24]. Available from: https://www.canada.ca/en/health-canada/services/drug-health-product-review-approval/submissions-under-review.html
  • Sato T, Issa JJ, Kropf P. DNA hypomethylating drugs in cancer therapy. Cold Spring Harb Perspect Med. 2017;7(5). pii:a026948
  • Plass C, Pfister SM, Lindroth AM, et al. Mutations in regulators of the epigenome and their connections to global chromatin patterns in cancer. Nat Rev Genet. 2013;14:765–780.
  • Creusot F, Acs G, Christman JK. Inhibition of DNA methyltransferase and induction of Friend erythroleukemia cell differentiation by 5-azacytidine and 5-aza-2ʹ-deoxycytidine. J Biol Chem. 1982;257:2041–2048.
  • Wilson VL, Jones PA, Momparler RL. Inhibition of DNA methylation in L1210 leukemic cells by 5-aza-2ʹ-deoxycytidine as a possible mechanism of chemotherapeutic action. Cancer Res. 1983;43:3493–3496.
  • Jones PA, Taylor SM. Cellular differentiation, cytidine analogs and DNA methylation. Cell. 1980;20:85–93.
  • Bejar R, Lord A, Stevenson K, et al. TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients. Blood. 2014;124:2705–2712.
  • Traina F, Visconte V, Elson P, et al. Impact of molecular mutations on treatment response to DNMT inhibitors in myelodysplasia and related neoplasms. Leukemia. 2014;28:78–87.
  • Kuendgen A, Muller-Thomas C, Lauseker M, et al. Efficacy of azacitidine is independent of molecular and clinical characteristics - an analysis of 128 patients with myelodysplastic syndromes or acute myeloid leukemia and a review of the literature. Oncotarget. 2018;9:27882–27894.
  • Duchmann M, Yalniz FF, Sanna A, et al. Prognostic role of gene mutations in chronic myelomonocytic leukemia patients treated with hypomethylating agents. EBioMedicine. 2018;31:174–181.
  • Jung SH, Kim YJ, Yim SH, et al. Somatic mutations predict outcomes of hypomethylating therapy in patients with myelodysplastic syndrome. Oncotarget. 2016;7:55264–55275.
  • Cedena MT, Rapado I, Santos-Lozano A, et al. Mutations in the DNA methylation pathway and number of driver mutations predict response to azacitidine in myelodysplastic syndromes. Oncotarget. 2017;8:106948–106961.
  • Meldi K, Qin T, Buchi F, et al. Specific molecular signatures predict decitabine response in chronic myelomonocytic leukemia. J Clin Invest. 2015;125:1857–1872.
  • Chung W, Kelly AD, Kropf P, et al. Genomic and epigenomic predictors of response to guadecitabine in relapsed/refractory acute myelogenous leukemia. Clin Epigenetics. 2019;11:106.
  • Welch JS, Petti AA, Miller CA, et al. TP53 and decitabine in acute myeloid leukemia and myelodysplastic syndromes. N Engl J Med. 2016;375:2023–2036.
  • Chang CK, Zhao YS, Xu F, et al. TP53 mutations predict decitabine-induced complete responses in patients with myelodysplastic syndromes. Br J Haematol. 2017;176:600–608.
  • Boddu P, Kantarjian H, Ravandi F, et al. Outcomes with lower intensity therapy in TP53-mutated acute myeloid leukemia. Leuk Lymphoma. 2018;59:2238–2241.
  • Takahashi K, Patel K, Bueso-Ramos C, et al. Clinical implications of TP53 mutations in myelodysplastic syndromes treated with hypomethylating agents. Oncotarget. 2016;7:14172–14187.
  • Kadia TM, Jain P, Ravandi F, et al. TP53 mutations in newly diagnosed acute myeloid leukemia: clinicomolecular characteristics, response to therapy, and outcomes. Cancer. 2016;122:3484–3491.
  • Short NJ, Kantarjian HM, Loghavi S, et al. Treatment with a 5-day versus a 10-day schedule of decitabine in older patients with newly diagnosed acute myeloid leukaemia: a randomised phase 2 trial. Lancet Haematol. 2019;6:e29–e37.
  • Griffiths EA, Choy G, Redkar S, et al. SGI-110: DNA methyltransferase inhibitor oncolytic. Drugs Future. 2013;38:535–543.
  • Kantarjian HM, Roboz GJ, Kropf PL, et al. Guadecitabine (SGI-110) in treatment-naive patients with acute myeloid leukaemia: phase 2 results from a multicentre, randomised, phase 1/2 trial. Lancet Oncol. 2017;18:1317–1326.
  • Issa JJ, Roboz G, Rizzieri D, et al. Safety and tolerability of guadecitabine (SGI-110) in patients with myelodysplastic syndrome and acute myeloid leukaemia: a multicentre, randomised, dose-escalation phase 1 study. Lancet Oncol. 2015;16:1099–1110.
  • Shen L, Kondo Y, Guo Y, et al. Genome-wide profiling of DNA methylation reveals a class of normally methylated CpG island promoters. PLoS Genet. 2007;3:2023–2036.
  • Roboz GJ, Kantarjian HM, Yee KWL, et al. Dose, schedule, safety, and efficacy of guadecitabine in relapsed or refractory acute myeloid leukemia. Cancer. 2018;124:325–334.
  • Stahl M, DeVeaux M, Montesinos P, et al. Hypomethylating agents in relapsed and refractory AML: outcomes and their predictors in a large international patient cohort. Blood Adv. 2018;2:923–932.
  • Blum W, Garzon R, Klisovic RB, et al. Clinical response and miR-29b predictive significance in older AML patients treated with a 10-day schedule of decitabine. Proc Natl Acad Sci U S A. 2010;107:7473–7478.
  • 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;126:291–299.
  • Fenaux P, Gobbi M, Kropf PL, et al. Results of ASTRAL-1 study, a phase 3 randomized trial of guadecitabine (G) vs treatment choice (TC) in treatment naive acute myeloid leukemia (TN-AML) not eligible for intensive chemotherapy (IC). HemaSphere. 2019;3:394–395.
  • Mozessohn L, Cheung MC, Fallahpour S, et al. Azacitidine in the ‘real-world’: an evaluation of 1101 higher-risk myelodysplastic syndrome/low blast count acute myeloid leukaemia patients in Ontario, Canada. Br J Haematol. 2018;181:803–815.
  • Sallman DA, Komrokji R, Vaupel C, et al. Impact of TP53 mutation variant allele frequency on phenotype and outcomes in myelodysplastic syndromes. Leukemia. 2016;30:666–673.
  • Haase D, Stevenson KE, Neuberg D, et al. TP53 mutation status divides myelodysplastic syndromes with complex karyotypes into distinct prognostic subgroups. Leukemia. 2019;33:1747–1758.
  • Rucker FG, Schlenk RF, Bullinger L, et al. TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome. Blood. 2012;119:2114–2121.
  • Kulasekararaj AG, Smith AE, Mian SA, et al. TP53 mutations in myelodysplastic syndrome are strongly correlated with aberrations of chromosome 5, and correlate with adverse prognosis. Br J Haematol. 2013;160:660–672.
  • Desoutter J, Gay J, Berthon C, et al. Molecular prognostic factors in acute myeloid leukemia receiving first-line therapy with azacitidine. Leukemia. 2016;30:1416–1418.
  • Bally C, Ades L, Renneville A, et al. Prognostic value of TP53 gene mutations in myelodysplastic syndromes and acute myeloid leukemia treated with azacitidine. Leuk Res. 2014;38:751–755.
  • Huls G, Suciu S, Wijermans P, et al. 10-day vs 5-day decitabine: equivalence cannot be concluded. Lancet Haematol. 2019;6:e177.
  • Short NJ, Ravandi F. 10-day vs 5-day decitabine: equivalence cannot be concluded - Authors’ reply. Lancet Haematol. 2019;6:e178.
  • Freed-Pastor WA, Prives C. Mutant p53: one name, many proteins. Genes Dev. 2012;26:1268–1286.
  • Naqvi K, Nogueras Gonzalez G, Cheung C, et al. Randomized phase II study of guadecitabine (SGI-110) based regimens comparing guadecitabine 5 days (SGI5), 10 days (SGI10), 5 days + idarubicin (SGI5 + Ida), and 5 days + cladribine (SGI5 + Clad), in previously untreated patients ≥ 70 years with acute myeloid leukemia (AML) – a Bayesian design. Clin Lymphoma Myeloma Leuk. 2017;17:S6.
  • Mesa RA, Li CY, Ketterling RP, et al. Leukemic transformation in myelofibrosis with myeloid metaplasia: a single-institution experience with 91 cases. Blood. 2005;105:973–977.
  • Tefferi A, Mudireddy M, Mannelli F, et al. Blast phase myeloproliferative neoplasm: mayo-AGIMM study of 410 patients from two separate cohorts. Leukemia. 2018;32:1200–1210.
  • Kennedy JA, Atenafu EG, Messner HA, et al. Treatment outcomes following leukemic transformation in Philadelphia-negative myeloproliferative neoplasms. Blood. 2013;121:2725–2733.
  • Andriani A, Montanaro M, Voso MT, et al. Azacytidine for the treatment of retrospective analysis from the Gruppo Laziale for the study of Ph-negative MPN. Leuk Res. 2015;39:801–804.
  • Badar T, Kantarjian HM, Ravandi F, et al. Therapeutic benefit of decitabine, a hypomethylating agent, in patients with high-risk primary myelofibrosis and myeloproliferative neoplasm in accelerated or blastic/acute myeloid leukemia phase. Leuk Res. 2015;39:950–956.
  • Mascarenhas J, Navada S, Malone A, et al. Therapeutic options for patients with myelofibrosis in blast phase. Leuk Res. 2010;34:1246–1249.
  • Thepot S, Itzykson R, Seegers V et al. Treatment of progression of Philadelphia-negative myeloproliferative neoplasms to myelodysplastic syndrome or acute myeloid leukemia by azacitidine: a report on 54 cases on the behalf of the Groupe Francophone des Myelodysplasies (GFM). Blood 2010; 116: 3735–3742.
  • Grinfeld J, Nangalia J, Baxter EJ, et al. Classification and personalized prognosis in myeloproliferative neoplasms. N Engl J Med. 2018;379:1416–1430.
  • Rampal R, Ahn J, Abdel-Wahab O, et al. Genomic and functional analysis of leukemic transformation of myeloproliferative neoplasms. Proc Natl Acad Sci U S A. 2014;111:E5401–5410.
  • Rampal RK, Mascarenhas JO, Kosiorek HE, et al. Safety and efficacy of combined ruxolitinib and decitabine in accelerated and blast-phase myeloproliferative neoplasms. Blood Adv. 2018;2:3572–3580.
  • Bose P, Verstovsek S, Gasior Y, et al. Phase I/II study of ruxolitinib (RUX) with decitabine (DAC) in patients with post-myeloproliferative neoplasm acute myeloid leukemia (post-MPN AML): phase I results. Blood. 2016;128:4262.
  • Harutyunyan A, Klampfl T, Cazzola M, et al. p53 lesions in leukemic transformation. N Engl J Med. 2011;364:488–490.
  • Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–674.
  • Holmstrom MO, Hasselbalch HC. Cancer immune therapy for myeloid malignancies: present and future. Semin Immunopathol. 2019;41:97–109.
  • Yang H, Bueso-Ramos C, DiNardo C, et al. Expression of PD-L1, PD-L2, PD-1 and CTLA4 in myelodysplastic syndromes is enhanced by treatment with hypomethylating agents. Leukemia. 2014;28:1280–1288.
  • Daver N, Garcia-Manero G, Basu S, et al. Efficacy, safety, and biomarkers of response to azacitidine and nivolumab in relapsed/refractory acute myeloid leukemia: a non-randomized, open-label, phase 2 study. Cancer Discov. 2018;9(3):370–383.
  • Saleh MH, Wang L, Goldberg MS. Improving cancer immunotherapy with DNA methyltransferase inhibitors. Cancer Immunol Immunother. 2016;65:787–796.
  • Coral S, Parisi G, Nicolay HJ, et al. Immunomodulatory activity of SGI-110, a 5-aza-2ʹ-deoxycytidine-containing demethylating dinucleotide. Cancer Immunol Immunother. 2013;62:605–614.
  • Srivastava P, Paluch BE, Matsuzaki J, et al. Immunomodulatory action of SGI-110, a hypomethylating agent, in acute myeloid leukemia cells and xenografts. Leuk Res. 2014;38:1332–1341.
  • Luo N, Nixon MJ, Gonzalez-Ericsson PI, et al. DNA methyltransferase inhibition upregulates MHC-I to potentiate cytotoxic T lymphocyte responses in breast cancer. Nat Commun. 2018;9:248.
  • Yang H, Fang Z, Clise-Dwyer K, et al. Induced PD-1 expression on bone marrow CD34+ cells from MDS patients treated with 5-azacitadine in combination with nivolumab and/or ipilimumab. Blood. 2018;132:1807.
  • Suzman DL, Agrawal S, Ning YM, et al. FDA approval summary: atezolizumab or pembrolizumab for the treatment of patients with advanced urothelial carcinoma ineligible for cisplatin-containing chemotherapy. Oncologist. 2018; 24(4):563–569.
  • First anti-PD-L1 drug approved for NSCLC. Cancer Discov. 2016;6:OF1.
  • Wingard JR, Majhail NS, Brazauskas R, et al. Long-term survival and late deaths after allogeneic hematopoietic cell transplantation. J Clin Oncol. 2011;29:2230–2239.
  • Soiffer RJ, Chen YB. Pharmacologic agents to prevent and treat relapse after allogeneic hematopoietic cell transplantation. Blood Adv. 2017;1:2473–2482.
  • Dietz AC, Wayne AS. Cells to prevent/treat relapse following allogeneic stem cell transplantation. Hematology Am Soc Hematol Educ Program. 2017;2017:708–715.
  • Schroeder T, Rachlis E, Bug G, et al. Treatment of acute myeloid leukemia or myelodysplastic syndrome relapse after allogeneic stem cell transplantation with azacitidine and donor lymphocyte infusions–a retrospective multicenter analysis from the German Cooperative Transplant Study Group. Biol Blood Marrow Transplant. 2015;21:653–660.
  • Schroeder T, Rautenberg C, Kruger W, et al. Treatment of relapsed AML and MDS after allogeneic stem cell transplantation with decitabine and DLI-a retrospective multicenter analysis on behalf of the German cooperative transplant study group. Ann Hematol. 2018;97:335–342.
  • Steinmann J, Bertz H, Wasch R, et al. 5-Azacytidine and DLI can induce long-term remissions in AML patients relapsed after allograft. Bone Marrow Transplant. 2015;50:690–695.
  • Sommer S, Cruijsen M, Claus R, et al. Decitabine in combination with donor lymphocyte infusions can induce remissions in relapsed myeloid malignancies with higher leukemic burden after allogeneic hematopoietic cell transplantation. Leuk Res. 2018;72:20–26.
  • Garcia-Manero G, Sasaki K, Montalban-Bravo G, et al. Final report of a phase II study of guadecitabine (SGI-110) in patients (pts) with previously untreated myelodysplastic syndrome (MDS). Blood. 2018;132:232.
  • Borthakur G, Ahdab SE, Ravandi F, et al. Activity of decitabine in patients with myelodysplastic syndrome previously treated with azacitidine. Leuk Lymphoma. 2008;49:690–695.
  • Harel S, Cherait A, Berthon C, et al. Outcome of patients with high risk myelodysplastic syndrome (MDS) and advanced chronic myelomonocytic leukemia (CMML) treated with decitabine after azacitidine failure. Leuk Res. 2015;39:501–504.
  • Komrokji RS, Apuri S, Al Ali N, et al. Evidence for selective benefit of sequential treatment with azanucleosides in patients with myelodysplastic syndromes (MDS). J Clin Oncol. 2013;31:7113.
  • Garcia-Manero G, Ritchie EK, Walsh KJ, et al. Long term results of a randomized phase 2 dose-response study of guadecitabine, a novel subcutaneous (sc) hypomethylating agent (HMA), in 102 patients with intermediate or high risk myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML). Blood. 2018;132:231.
  • Sebert M, Renneville A, Bally C, et al. A phase II study of guadecitabine in higher-risk myelodysplastic syndrome and low blast count acute myeloid leukemia after azacitidine failure. Haematologica. 2019;104(8):1565–1571.
  • Garcia-Manero G, Roboz G, Walsh K, et al. Guadecitabine (SGI-110) in patients with intermediate or high-risk myelodysplastic syndromes: phase 2 results from a multicentre, open-label, randomised, phase 1/2 trial. Lancet Haematol. 2019;6:e317–e327.
  • O’Connell CL, Kropf PL, Punwani N, et al. Phase I results of a multicenter clinical trial combining guadecitabine, a DNA methyltransferase inhibitor, with atezolizumab, an immune checkpoint inhibitor, in patients with relapsed or refractory myelodysplastic syndrome or chronic myelomonocytic leukemia. Blood. 2018;132:1811.
  • Wei AH, Strickland SA Jr., Hou JZ, et al. Venetoclax combined with low-dose cytarabine for previously untreated patients with acute myeloid leukemia: results from a phase Ib/II study. J Clin Oncol. 2019;37:1277–1284.
  • DiNardo CD, Rausch CR, Benton C, et al. Clinical experience with the BCL2-inhibitor venetoclax in combination therapy for relapsed and refractory acute myeloid leukemia and related myeloid malignancies. Am J Hematol. 2018;93:401–407.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.