Therapeutic approaches for the management of higher risk myelodysplastic syndromes

References

• Greenberg P, Cox C, LeBeau MM, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997;89(6):2079–2088.
   PubMed Web of Science ®Google Scholar
• Greenberg PL, Tuechler H, Schanz J, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012;120(12):2454–2465.
   PubMed Web of Science ®Google Scholar
• Hiwase DK, Singhal D, Strupp C, et al. Dynamic assessment of RBC-transfusion dependency improves the prognostic value of the revised-IPSS in MDS patients. Am J Hematol. 2017;92(6):508–514.
   PubMed Web of Science ®Google Scholar
• Benton CB, Khan M, Sallman D, et al. Prognosis of patients with intermediate risk IPSS-R myelodysplastic syndrome indicates variable outcomes and need for models beyond IPSS-R. Am J Hematol. 2018;93(10):1245–1253.
   PubMed Web of Science ®Google Scholar
• Pfeilstöcker M, Tuechler H, Sanz G, et al. Time-dependent changes in mortality and transformation risk in MDS. Blood. 2016;128(7):902–910.
   PubMed Web of Science ®Google Scholar
• Kantarjian H, O'Brien S, Ravandi F, et al. Proposal for a new risk model in myelodysplastic syndrome that accounts for events not considered in the original international prognostic scoring system. Cancer. 2008;113(6):1351–1361.
   PubMed Web of Science ®Google Scholar
• Daver N, Naqvi K, Jabbour E, et al. Impact of comorbidities by ACE-27 in the revised-IPSS for patients with myelodysplastic syndromes. Am J Hematol. 2014;89(5):509–516.
   PubMed Web of Science ®Google Scholar
• Starkman R, Alibhai S, Wells RA, et al. An MDS-specific frailty index based on cumulative deficits adds independent prognostic information to clinical prognostic scoring. Leukemia. 2020;34(5):1394–1406.
   PubMed Web of Science ®Google Scholar
• Bejar R, Stevenson K, Abdel-Wahab O, et al. Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med. 2011;364(26):2496–2506.
   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; quiz 3699.
   PubMed Web of Science ®Google Scholar
• Nazha A, Komrokji R, Meggendorfer M, et al. Personalized prediction model to risk stratify patients with myelodysplastic syndromes. J Clin Oncol. 2021;39(33):3737–3746.
   PubMed Web of Science ®Google Scholar
• Bernard E, Tuechler H, Greenberg PL, et al. Molecular international prognostic scoring system for myelodysplastic syndromes. NEJM Evidence. 2022;1(7).
   PubMedGoogle Scholar
• Grob T, Al Hinai AS, Sanders MA, et al. Molecular characterization of mutant tp53 acute myeloid leukemia and high-risk myelodysplastic syndrome. Blood. 2022;139(15):2347–2354.
   PubMed Web of Science ®Google Scholar
• Arber DA, Orazi A, Hasserjian RP, et al. International consensus classification of myeloid neoplasms and acute leukemia: integrating morphological, clinical, and genomic data. Blood. 2022;140(11):1200–1228.
   PubMed Web of Science ®Google Scholar
• Estey E, Hasserjian RP, Döhner H. Distinguishing AML from MDS: a fixed blast percentage may no longer be optimal. Blood. 2022;139(3):323–332.
   PubMed Web of Science ®Google Scholar
• Weinberg OK, Siddon A, Madanat YF, et al. TP53 mutation defines a unique subgroup within complex karyotype de novo and therapy-related MDS/AML. Blood Adv. 2022;6(9):2847–2853.
   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
• 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
• Kantarjian H, Issa J-PJ, 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
• Lübbert M, Suciu S, Baila L, 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
• Kantarjian H, Oki Y, Garcia-Manero G, et al. Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood. 2007;109(1):52–57.
   PubMed Web of Science ®Google Scholar
• Zeidan AM, Stahl M, Hu X, et al. Long-term survival of older patients with MDS treated with HMA therapy without subsequent stem cell transplantation. Blood. 2018;131(7):818–821.
   PubMed Web of Science ®Google Scholar
• Bejar R, Lord A, Stevenson K, et al. TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients. Blood. 2014;124(17):2705–2712.
   PubMed Web of Science ®Google Scholar
• Welch JS, Petti AA, Miller CA, et al. TP53 and decitabine in acute myeloid leukemia and myelodysplastic syndromes. N Engl J Med. 2016;375(21):2023–2036.
   PubMed Web of Science ®Google Scholar
• Liu Y-C, Kwon J, Fabiani E, et al. Demethylation and up-regulation of an oncogene after hypomethylating therapy. N Engl J Med. 2022;386(21):1998–2010.
   PubMed Web of Science ®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. Blood. 2019;134(Supplement_1):846–846.
   PubMed Web of Science ®Google Scholar
• Garcia-Manero G, Gore SD, 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
• 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):1426–1436.
   PubMed Web of Science ®Google Scholar
• Ramsey HE, Oganesian A, Gorska AE, et al. Oral azacitidine and cedazuridine approximate parenteral azacitidine efficacy in murine model. Target Oncol. 2020;15(2):231–240.
   PubMed Web of Science ®Google Scholar
• Kantarjian H, O'brien S, Cortes J, et al. Results of intensive chemotherapy in 998 patients age 65 years or older with acute myeloid leukemia or high-risk myelodysplastic syndrome: predictive prognostic models for outcome. Cancer. 2006;106(5):1090–1098.
   PubMed Web of Science ®Google Scholar
• 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(3):666–673.
   PubMed Web of Science ®Google Scholar
• Lancet JE, Uy GL, Cortes JE, et al. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol. 2018;36(26):2684–2692.
   PubMed Web of Science ®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(Supplement 1):243–243.
   Google Scholar
• Jacoby MA, Sallman DA, Scott BL, et al. A pilot study of CPX-351 (VYXEOS©) for transplant eligible, higher risk patients with myelodysplastic syndrome. Blood. 2021;138(Supplement 1):540–540.
   Google Scholar
• Robin M, Porcher R, Adès L, et al. HLA-matched allogeneic stem cell transplantation improves outcome of higher risk myelodysplastic syndrome a prospective study on behalf of SFGM-TC and GFM. Leukemia. 2015;29(7):1496–1501.
   PubMed Web of Science ®Google Scholar
• Nakamura R, Saber W, Martens MJ, et al. Biologic assignment trial of Reduced-Intensity hematopoietic cell transplantation based on donor availability in patients 50–75 years of age with advanced myelodysplastic syndrome. J Clin Oncol. 2021;39(30):3328–3339.
   PubMed Web of Science ®Google Scholar
• Schroeder T, Wegener N, Lauseker M, et al. Comparison between upfront transplantation and different pretransplant cytoreductive treatment approaches in patients with high-risk myelodysplastic syndrome and secondary acute myelogenous leukemia. Biol Blood Marrow Transplant. 2019;25(8):1550–1559.
   PubMed Web of Science ®Google Scholar
• Damaj G, Duhamel A, Robin M, et al. Impact of azacitidine before allogeneic stem-cell transplantation for myelodysplastic syndromes: a study by the société française de greffe de moelle et de Thérapie-Cellulaire and the Groupe-Francophone des myélodysplasies. J Clin Oncol. 2012;30(36):4533–4540.
   PubMed Web of Science ®Google Scholar
• Kröger N, Sockel K, Wolschke C, et al. Comparison between 5-Azacytidine treatment and allogeneic stem-cell transplantation in elderly patients with advanced MDS according to donor availability (VidazaAllo study). J Clin Oncol. 2021;39(30):3318–3327.
   PubMed Web of Science ®Google Scholar
• Yun S, Geyer SM, Komrokji RS, et al. Prognostic significance of serial molecular annotation in myelodysplastic syndromes (MDS) and secondary acute myeloid leukemia (sAML). Leukemia. 2021;35(4):1145–1155.
   PubMed Web of Science ®Google Scholar
• Hunter AM, Komrokji RS, Yun S, et al. Baseline and serial molecular profiling predicts outcomes with hypomethylating agents in myelodysplastic syndromes. Blood Adv. 2021;5(4):1017–1028.
   PubMed Web of Science ®Google Scholar
• de Witte T, Bowen D, Robin M, et al. Allogeneic hematopoietic stem cell transplantation for MDS and CMML: recommendations from an international expert panel. Blood. 2017;129(13):1753–1762.
   PubMed Web of Science ®Google Scholar
• Medeiros BC, Fathi AT, DiNardo CD, et al. Isocitrate dehydrogenase mutations in myeloid malignancies. Leukemia. 2017;31(2):272–281.
   PubMed Web of Science ®Google Scholar
• Thol F, Weissinger EM, Krauter J, et al. IDH1 mutations in patients with myelodysplastic syndromes are associated with an unfavorable prognosis. Haematologica. 2010;95(10):1668–1674.
   PubMed Web of Science ®Google Scholar
• Kosmider O, Gelsi-Boyer V, Slama L, et al. Mutations of IDH1 and IDH2 genes in early and accelerated phases of myelodysplastic syndromes and MDS/myeloproliferative neoplasms. Leukemia. 2010;24(5):1094–1096.
   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.
   PubMed Web of Science ®Google Scholar
• Komrokji RS, Al Ali N, Chan O, et al. IDH mutations are enriched in myelodysplastic syndromes patients with severe neutropenia: a potential targeted therapy. Blood. 2021;138(Supplement 1):1526–1526.
   Google Scholar
• Sebert M, Cluzeau T, Beyne Rauzy O, 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):62–62.
   Google Scholar
• Venugopal S, Dinardo CD, Takahashi K, et al. Phase II study of the IDH2-inhibitor enasidenib in patients with high-risk IDH2-mutated myelodysplastic syndromes (MDS). J Clin Oncol. 2021;39(15_suppl):7010–7010.
   Web of Science ®Google Scholar
• Montesinos P, Recher C, Vives S, et al. Ivosidenib and azacitidine in IDH1-mutated acute myeloid leukemia. N Engl J Med. 2022;386(16):1519–1531.
   PubMed Web of Science ®Google Scholar
• Daver N, Strati P, Jabbour E, et al. FLT3 mutations in myelodysplastic syndrome and chronic myelomonocytic leukemia. Am J Hematol. 2013;88(1):56–59.
   PubMed Web of Science ®Google Scholar
• Xu F, Han R, Zhang J, et al. The role of FLT3-ITD mutation on de novo MDS in Chinese population. Clin Lymphoma Myeloma Leuk. 2019;19(2):e107–e115.
   PubMed Web of Science ®Google Scholar
• Fischer T, Stone RM, Deangelo DJ, et al. Phase IIB trial of oral midostaurin (PKC412), the FMS-like tyrosine kinase 3 receptor (FLT3) and multi-targeted kinase inhibitor, in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome with either wild-type or mutated FLT3. J Clin Oncol. 2010;28(28):4339–4345.
   PubMed Web of Science ®Google Scholar
• Strati P, Kantarjian H, Ravandi F, et al. Phase I/II trial of the combination of midostaurin (PKC412) and 5-azacytidine for patients with acute myeloid leukemia and myelodysplastic syndrome. Am J Hematol. 2015;90(4):276–281.
   PubMed Web of Science ®Google Scholar
• Abuasab T, Jabbour EJ, Short NJ, et al. Initial results of phase I/II study of azacitidine in combination with quizartinib for patients with myelodysplastic syndrome and myelodysplastic/myeloproliferative neoplasm with FLT3 or CBL mutations. Blood. 2021;138(Supplement 1):1536–1536.
   Google Scholar
• Obeng EA, Chappell RJ, Seiler M, et al. Physiologic expression of Sf3b1(K700E) causes impaired erythropoiesis, aberrant splicing, and sensitivity to therapeutic spliceosome modulation. Cancer Cell. 2016;30(3):404–417.
   PubMed Web of Science ®Google Scholar
• Lee SC-W, Dvinge H, Kim E, et al. Modulation of splicing catalysis for therapeutic targeting of leukemia with mutations in genes encoding spliceosomal proteins. Nat Med. 2016;22(6):672–678.
   PubMed Web of Science ®Google Scholar
• Seiler M, Yoshimi A, Darman R, et al. H3B-8800, an orally available small-molecule splicing modulator, induces lethality in spliceosome-mutant cancers. Nat Med. 2018;24(4):497–504.
   PubMed Web of Science ®Google Scholar
• Smith MA, Choudhary GS, Pellagatti A, et al. U2AF1 mutations induce oncogenic IRAK4 isoforms and activate innate immune pathways in myeloid malignancies. Nat Cell Biol. 2019;21(5):640–650.
   PubMed Web of Science ®Google Scholar
• Choudhary GS, Smith MA, Pellagatti A, et al. SF3B1 mutations induce oncogenic IRAK4 isoforms and activate targetable innate immune pathways in MDS and AML. Blood. 2019;134(Supplement_1):4224–4224.
   Google Scholar
• Garcia-Manero G, Winer ES, DeAngelo DJ, et al. Phase 1/2a study of the IRAK4 inhibitor CA-4948 as monotherapy or in combination with azacitidine or venetoclax in patients with relapsed/refractory (R/R) acute myeloid leukemia or lyelodysplastic syndrome. J Clin Oncol. 2022;40(16_suppl):7016–7016.
   Web of Science ®Google Scholar
• Kuendgen A, Lauseker M, List AF, et al. Lenalidomide does not increase AML progression risk in RBC transfusion-dependent patients with low- or intermediate-1-risk MDS with del(5q): a comparative analysis. Leukemia. 2013;27(5):1072–1079.
   PubMed Web of Science ®Google Scholar
• Adès L, Boehrer S, Prebet T, et al. Efficacy and safety of lenalidomide in intermediate-2 or high-risk myelodysplastic syndromes with 5q deletion: results of a phase 2 study. Blood. 2009;113(17):3947–3952.
   PubMed Web of Science ®Google Scholar
• Kenealy M, Hertzberg M, Benson W, et al. Azacitidine with or without lenalidomide in higher risk myelodysplastic syndrome & low blast acute myeloid leukemia. Haematologica. 2019;104(4):700–709.
   PubMed Web of Science ®Google Scholar
• Rasmussen B, Göhring G, Bernard E, et al. Randomized phase II study of azacitidine ± lenalidomide in higher-risk myelodysplastic syndromes and acute myeloid leukemia with a karyotype including del(5q). Leukemia. 2022;36(5):1436–1439.
   PubMed Web of Science ®Google Scholar
• List A, Ebert BL, Fenaux P. A decade of progress in myelodysplastic syndrome with chromosome 5q deletion. Leukemia. 2018;32(7):1493–1499.
   PubMed Web of Science ®Google Scholar
• Jädersten M, Saft L, Smith A, et al. TP53 mutations in low-risk myelodysplastic syndromes with del(5q) predict disease progression. J Clin Oncol. 2011;29(15):1971–1979.
   PubMed Web of Science ®Google Scholar
• Pedersen-Bjergaard J, Andersen MK, Andersen MT, et al. Genetics of therapy-related myelodysplasia and acute myeloid leukemia. Leukemia. 2008;22(2):240–248.
   PubMed Web of Science ®Google Scholar
• Haase D, Stevenson KE, Neuberg D, et al. TP53 mutation status divides myelodysplastic syndromes with complex karyotypes into distinct prognostic subgroups. Leukemia. 2019;33(7):1747–1758.
   PubMed Web of Science ®Google Scholar
• 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(5):660–672.
   PubMed Web of Science ®Google Scholar
• Swoboda DM, Kanagal-Shamanna R, Brunner AM, et al. Marrow ring sideroblasts are highly predictive for TP53 mutation in MDS with excess blasts. Leukemia. 2022;36(4):1189–1192.
   PubMed Web of Science ®Google Scholar
• Bernard E, Nannya Y, Hasserjian RP, et al. Implications of TP53 allelic state for genome stability, clinical presentation and outcomes in myelodysplastic syndromes. Nat Med. 2020;26(10):1549–1556.
   PubMed Web of Science ®Google Scholar
• Lambert JMR, Gorzov P, Veprintsev DB, et al. PRIMA-1 reactivates mutant p53 by covalent binding to the core domain. Cancer Cell. 2009;15(5):376–388.
   PubMed Web of Science ®Google Scholar
• Maslah N, Salomao N, Drevon L, et al. Synergistic effects of PRIMA-1Met (APR-246) and 5-azacitidine in TP53-mutated myelodysplastic syndromes and acute myeloid leukemia. Haematologica. 2020;105(6):1539–1551.
   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;39(14):1584–1594.
   PubMed Web of Science ®Google Scholar
• Cluzeau T, Sebert M, Rahmé R, et al. Eprenetapopt plus azacitidine in TP53-Mutated myelodysplastic syndromes and acute myeloid leukemia: a phase II study by the groupe francophone des myélodysplasies (GFM). J Clin Oncol. 2021;39(14):1575–1583. JCO2002342.
   PubMed Web of Science ®Google Scholar
• Sallman DA, Komrokji RS, DeZern AE, et al. Long term follow-up and combined phase 2 results of eprenetapopt (APR-246) and azacitidine (AZA) in patients with TP53 mutant myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia (AML). Blood. 2021;138(Supplement 1):246–246.
   PubMedGoogle Scholar
• Mishra A, Tamari R, DeZern AE, et al. Eprenetapopt plus azacitidine after allogeneic hematopoietic stem-cell transplantation for TP53-Mutant acute myeloid leukemia and myelodysplastic syndromes. J Clin Oncol. 2022; JCO2200181.
   Web of Science ®Google Scholar
• Corey SJ, Minden MD, Barber DL, et al. Myelodysplastic syndromes: the complexity of stem-cell diseases. Nat Rev Cancer. 2007;7(2):118–129.
   PubMed Web of Science ®Google Scholar
• Jilg S, Reidel V, Müller-Thomas C, et al. Blockade of BCL-2 proteins efficiently induces apoptosis in progenitor cells of high-risk myelodysplastic syndromes patients. Leukemia. 2016;30(1):112–123.
   PubMed Web of Science ®Google Scholar
• Wei AH, Garcia JS, Borate U, et al. MDS-158: Updated safety and efficacy of venetoclax in combination with azacitidine for the treatment of patients with Treatment-Naïve, Higher-Risk myelodysplastic syndromes: Phase 1b results. Clin Lymphoma Myeloma Leukemia. 2021;21:S343.
   Web of Science ®Google Scholar
• Zeidan AM, Pollyea DA, Garcia JS, et al. A phase 1b study evaluating the safety and efficacy of venetoclax as monotherapy or in combination with azacitidine for the treatment of relapsed/refractory myelodysplastic syndrome. Blood. 2019;134(Supplement_1):565–565.
   Web of Science ®Google Scholar
• Bogenberger JM, Kornblau SM, Pierceall WE, et al. BCL-2 family proteins as 5-azacytidine-sensitizing targets and determinants of response in myeloid malignancies. Leukemia. 2014;28(8):1657–1665.
   PubMed Web of Science ®Google Scholar
• Ball BJ, Famulare CA, Stein EM, et al. Venetoclax and hypomethylating agents (HMAs) induce high response rates in MDS, including patients after HMA therapy failure. Blood Adv. 2020;4(13):2866–2870.
   PubMed Web of Science ®Google Scholar
• Aldoss I, Zhang J, Pillai R, et al. Venetoclax and hypomethylating agents in TP53-mutated acute myeloid leukaemia. Br J Haematol. 2019;187(2):e45–e48.
   PubMed Web of Science ®Google Scholar
• Zeidan AM, Garcia JS, Fenaux P, et al. Phase 3 VERONA study of venetoclax with azacitidine to assess change in complete remission and overall survival in treatment-naïve higher-risk myelodysplastic syndromes. J Clin Oncol. 2021;39(15_suppl):TPS7054–TPS7054.
   Web of Science ®Google Scholar
• Zhou L, Jiang Y, Luo Q, et al. Neddylation: a novel modulator of the tumor microenvironment. Mol Cancer. 2019;18(1):77.
   PubMedGoogle Scholar
• Swords RT, Kelly KR, Smith PG, et al. Inhibition of NEDD8-activating enzyme: a novel approach for the treatment of acute myeloid leukemia. Blood. 2010;115(18):3796–3800.
   PubMed Web of Science ®Google Scholar
• Smith PG, Traore T, Grossman S, et al. Azacitidine/decitabine synergism with the NEDD8-activating enzyme inhibitor MLN4924 in Pre-Clinical AML models. Blood. 2011;118(21):578–578.
   Web of Science ®Google Scholar
• Sekeres MA, Watts J, Radinoff A, et al. Randomized phase 2 trial of pevonedistat plus azacitidine versus azacitidine for higher-risk MDS/CMML or low-blast AML. Leukemia. 2021;35(7):2119–2124.
   PubMed Web of Science ®Google Scholar
• Sekeres MA, Girshova L, Doronin VA, et al. Pevonedistat (PEV) + azacitidine (AZA) versus AZA alone as first-line treatment for patients with higher-risk myelodysplastic syndromes (MDS)/chronic myelomonocytic leukemia (CMML) or acute myeloid leukemia (AML) with 20–30% marrow blasts: the randomized phase 3 PANTHER trial (NCT03268954. Blood. 2021;138(Supplement 1):242–242.
   Google Scholar
• Adès L, Girshova L, Doronin VA, et al. Pevonedistat plus azacitidine vs azacitidine alone in higher-risk MDS/chronic myelomonocytic leukemia or low-blast percentage AML. Blood Adv. 2022; 6(17): 5132–5145.
   PubMed Web of Science ®Google Scholar
• 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(6):1280–1288.
   PubMed Web of Science ®Google Scholar
• Sallman DA, McLemore AF, Aldrich AL, et al. TP53 mutations in myelodysplastic syndromes and secondary AML confer an immunosuppressive phenotype. Blood. 2020;136(24):2812–2823.
   PubMed Web of Science ®Google Scholar
• Zeidan AM, Knaus HA, Robinson TM, et al. A multi-center phase I trial of ipilimumab in patients with myelodysplastic syndromes following hypomethylating agent failure. Clin Cancer Res. 2018;24(15):3519–3527.
   PubMed Web of Science ®Google Scholar
• Garcia-Manero G, Ribrag V, Zhang Y, et al. Pembrolizumab for myelodysplastic syndromes after failure of hypomethylating agents in the phase 1b KEYNOTE-013 study. Leuk Lymphoma. 2022;63(7):1660–1668.
   PubMed Web of Science ®Google Scholar
• Zeidan AM, Boss I, Beach CL, et al. A randomized phase 2 trial of azacitidine with or without durvalumab as first-line therapy for higher-risk myelodysplastic syndromes. Blood Adv. 2022;6(7):2207–2218.
   PubMed Web of Science ®Google Scholar
• Gerds AT, Scott BL, Greenberg P, et al. Atezolizumab alone or in combination did not demonstrate a favorable risk-benefit profile in myelodysplastic syndrome. Blood Adv. 2022;6(4):1152–1161.
   PubMed Web of Science ®Google Scholar
• Pang WW, Pluvinage JV, Price EA, et al. Hematopoietic stem cell and progenitor cell mechanisms in myelodysplastic syndromes. Proc Natl Acad Sci USA. 2013;110(8):3011–3016.
   PubMed Web of Science ®Google Scholar
• Jiang H, Fu R, Wang H, et al. CD47 is expressed abnormally on hematopoietic cells in myelodysplastic syndrome. Leuk Res. 2013;37(8):907–910.
   Google Scholar
• Boasman K, Bridle C, Simmonds MJ, et al. Role of pro-phagocytic calreticulin and anti-phagocytic CD47 in MDS AND MPN models treated with azacytidine or ruxolitinib; [cited 2021 Jul 2]. Available from: https://library.ehaweb.org/eha/2017/22nd/182624/kristian.boasman.role.of.pro-phagocytic.calreticulin.and.anti-phagocytic.cd47.html?f=listing%3D0%2Abrowseby%3D8%2Asortby%3D2%2Asearch%3Dcd47..
   Google Scholar
• Sallman DA, Malki MMA, Asch AS, et al. Magrolimab in combination with azacitidine for patients with untreated higher-risk myelodysplastic syndromes (HR MDS): 5F9005 phase 1B study results; [cited 2022 Aug 14].. Available from: https://library.ehaweb.org/eha/2022/eha2022-congress/357030/david.a.sallman.magrolimab.in.combination.with.azacitidine.for.patients.with.html?f=listing%3D0%2Abrowseby%3D8%2Asortby%3D2%2Asearch%3Dazacitidine
   Google Scholar
• de Back DZ, Kostova EB, van Kraaij M, et al. Of macrophages and red blood cells; a complex love story. Front Physiol. 2014;5:9.
   PubMed Web of Science ®Google Scholar
• Advani R, Flinn I, Popplewell L, et al. CD47 blockade by Hu5F9-G4 and rituximab in Non-Hodgkin’s lymphoma. N Engl J Med. 2018;379(18):1711–1721.
   PubMed Web of Science ®Google Scholar
• Asayama T, Tamura H, Ishibashi M, et al. Functional expression of tim-3 on blasts and clinical impact of its ligand galectin-9 in myelodysplastic syndromes. Oncotarget. 2017;8(51):88904–88917.
   PubMedGoogle Scholar
• Moskorz W, Cosmovici C, Jäger PS, et al. Myelodysplastic syndrome patients display alterations in their immune status reflected by increased PD-L1-expressing stem cells and highly dynamic exhausted T-cell frequencies. Br J Haematol. 2021;193(5):941–945.
   PubMed Web of Science ®Google Scholar
• Brunner AM, Esteve J, Porkka K, et al. Efficacy and safety of sabatolimab (MBG453) in combination with hypomethylating agents (HMAs) in patients (pts) with very high/High-Risk myelodysplastic syndrome (vHR/HR-MDS) and acute myeloid leukemia (AML): final analysis from a phase Ib study. Blood. 2021;138(Supplement 1):244–244.
   Google Scholar