Myelodysplastic syndrome and immunotherapy novel to next in-line treatments

References

• Pang WW, Pluvinage JV, Price EA, Sridhar K, Arber DA, Greenberg PL, Schrier SL, Park CY, Weissman IL. Hematopoietic stem cell and progenitor cell mechanisms in myelodysplastic syndromes. Proc Natl Acad Sci USA. 2013;110:3011–16. doi:10.1073/pnas.1222861110.
   PubMed Web of Science ®Google Scholar
• Garcia-Manero G. Myelodysplastic syndromes: 2012 update on diagnosis, risk-stratification, and management. Am J Hematol. 2012;87:692–701. doi:10.1002/ajh.23264.
   PubMed Web of Science ®Google Scholar
• Valent P, Horny H, Bennett JM, Fonatsch C, Germing U, Greenberg P, Haferlach T, Haase D, Kolb HJ, Krieger O, et al. Definitions and standards in the diagnosis and treatment of the myelodysplastic syndromes: consensus statements and report from a working conference. Leuk Res. 2007;31:727–36. doi:10.1016/j.leukres.2006.11.009.
   PubMed Web of Science ®Google Scholar
• Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, Sanz M, Vallespi T, Hamblin T, Oscier D, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997;89:2079–88.
   PubMed Web of Science ®Google Scholar
• Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Solé F, Bennett JM, Bowen D, Fenaux P, Dreyfus F, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012;120:2454–65. doi:10.1182/blood-2012-03-420489.
   PubMed Web of Science ®Google Scholar
• Nachtkamp K, Stark R, Strupp C, Kündgen A, Giagounidis A, Aul C, Hildebrandt B, Haas R, Gattermann N, Germing U, et al. Causes of death in 2877 patients with myelodysplastic syndromes. Ann Hematol. 2016;95:937–44. doi:10.1007/s00277-016-2649-3.
   PubMed Web of Science ®Google Scholar
• Stern M, De Wreede LC, Brand R, Van Biezen A, Dreger P, Mohty M, De Witte TM, Kröger N, Ruutu T. Sensitivity of hematological malignancies to graft-versus-host effects: an EBMT megafile analysis. Leukemia. 2014;28:2235–40. doi:10.1038/leu.2014.145.
   PubMed Web of Science ®Google Scholar
• Anderson JE, Appelbaum FR, Fisher LD, Schoch G, Shulman H, Anasetti C, Bensinger WI, Bryant E, Buckner CD, Doney K, et al. Allogeneic bone marrow transplantation for 93 patients with myelodysplastic syndrome. Blood. 1993;82:677–81. doi:10.1182/blood.V82.2.677.677.
   PubMed Web of Science ®Google Scholar
• Alessandrino EP, Della Porta MG, Bacigalupo A, Van Lint MT, Falda M, Onida F, Bernardi M, Iori AP, Rambaldi A, Cerretti R, et al. WHO classification and WPSS predict posttransplantation outcome in patients with myelodysplastic syndrome: a study from the Gruppo Italiano Trapianto di Midollo Osseo (GITMO). Blood. 2008;112:895–902. doi:10.1182/blood-2008-03-143735.
   PubMed Web of Science ®Google Scholar
• Anonymous The National Comprehensive Cancer Network. ® Myelodysplastic syndromes. (Version 1.2021); 2020 Nov 27.
   Google Scholar
• Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, Schoch R, Gattermann N, Sanz G, List A, 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;10:223–32. doi:10.1016/S1470-2045(09)70003-8.
   PubMed Web of Science ®Google Scholar
• Cheson BD, Greenberg PL, Bennett JM, Lowenberg B, Wijermans PW, Nimer SD, Pinto A, Beran M, De Witte TM, Stone RM, et al. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood. 2006;108:419–25. doi:10.1182/blood-2005-10-4149.
   PubMed Web of Science ®Google Scholar
• Seymour JF, Fenaux P, Silverman LR, Mufti GJ, Hellström-Lindberg E, Santini V, List AF, Gore SD, Backstrom J, et al. Effects of azacitidine compared with conventional care regimens in elderly (≥ 75 years) patients with higher-risk myelodysplastic syndromes. Crit Rev Oncol Hematol. 2010;76:218–27. doi:10.1016/j.critrevonc.2010.04.005.
   PubMed Web of Science ®Google Scholar
• Lübbert M, Suciu S, Baila L, Rüter BH, Platzbecker U, Giagounidis A, Selleslag D, Labar B, Germing U, Salih HR, 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. JCO. 2011;29:1987–96.
   PubMed Web of Science ®Google Scholar
• Prébet T, Gore SD, Esterni B, Gardin C, Itzykson R, Thepot S, Dreyfus F, Rauzy OB, Recher C, Adès L, et al. Outcome of high-risk myelodysplastic syndrome after azacitidine treatment failure. JCO. 2011;29:3322–27. doi:10.1200/JCO.2011.35.8135.
   PubMed Web of Science ®Google Scholar
• Kantarjian H, O’brien S, Cortes J, Giles F, Faderl S, Jabbour E, Garcia-Manero G, Wierda W, Pierce S, Shan 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;106:1090–98. doi:10.1002/cncr.21723.
   PubMed Web of Science ®Google Scholar
• Platzbecker U. Treatment of MDS. Blood. 2019;133:1096–107. doi:10.1182/blood-2018-10-844696.
   PubMed Web of Science ®Google Scholar
• Yang H, Bueso-Ramos C, DiNardo C, Estecio MR, Davanlou M, Geng QR, Fang Z, Nguyen M, Pierce S, Wei Y, et al. Expression of PD-L1, PD-L2, PD-1 and CTLA4 in myelodysplastic syndromes is enhanced by treatment with hypomethylating agents. Leukemia. 2013;28:1280–88. doi:10.1038/leu.2013.355.
   PubMed Web of Science ®Google Scholar
• Williams P, Basu S, Garcia-Manero G, Hourigan CS, Oetjen KA, Cortes JE, Ravandi F, Jabbour EJ, Al‐Hamal Z, Konopleva M, et al. The distribution of T-cell subsets and the expression of immune checkpoint receptors and ligands in patients with newly diagnosed and relapsed acute myeloid leukemia. Cancer. 2019;125:1470–81. doi:10.1002/cncr.31896.
   PubMed Web of Science ®Google Scholar
• Blank C, Mackensen A. Contribution of the PD-L1/PD-1 pathway to T-cell exhaustion: an update on implications for chronic infections and tumor evasion. Cancer Immunol Immunother. 2007;56:739–45. doi:10.1007/s00262-006-0272-1.
   PubMed Web of Science ®Google Scholar
• Bristol-Myers Squibb Company. OPDIVO (nivolumab). FDA; 2014 [accessed 2020 Oct 21]. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/125554s078lbl.pdf
   Google Scholar
• FDA package insert. Pembrolizumab prescribing information. 2020. <https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/125514s084lbl.pdf>
   Google Scholar
• Garcia-Manero G, Tallman MS, Martinelli G, Ribrag V, Yang H, Balakumaran A, Chlosta S, Zhang Y, Smith BD. Pembrolizumab, a PD-1 inhibitor, in patients with myelodysplastic syndrome (MDS) after failure of hypomethylating agent treatment. Blood. 2016;128:345–345. doi:10.1182/blood.V128.22.345.345.
   Web of Science ®Google Scholar
• Chien KS, Borthakur GM, Naqvi K, Daver NG, Cortes JE, DiNardo CD, Jabbour E, Andreeff M, Alvarado Y, Bose P, et al. Updated preliminary results from a phase II study combining azacitidine and pembrolizumab in patients with higher-risk myelodysplastic syndrome. Blood. 2019;134:4240–4240.
   Web of Science ®Google Scholar
• Bejar R, Stevenson K, Abdel-Wahab O, Galili N, Nilsson B, Garcia-Manero G, Kantarjian H, Raza A, Levine RL, Neuberg D. Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med. 2011;364:2496–506. doi:10.1056/NEJMoa1013343.
   PubMed Web of Science ®Google Scholar
• AstraZeneca. Durvalumab prescribing information. FDA; 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761069s018lbl.pdf
   Google Scholar
• Zeidan AM, Cavenagh J, Voso MT, Taussig D, Tormo M, Boss I, Copeland WB, Gray VE, Previtali A, O’ Connor T, et al. Efficacy and safety of azacitidine (AZA) in combination with the anti-PD-L1 durvalumab (durva) for the front-line treatment of older patients (pts) with Acute Myeloid Leukemia (AML) who are unfit for intensive chemotherapy (IC) and pts with higher-risk myelodysplastic syndromes (HR-MDS): results from a large, international, randomized phase 2 study. Blood. 2019;134:829–829.
   Web of Science ®Google Scholar
• Vereecque R, Saudemont A, Quesnel B. Cytosine arabinoside induces costimulatory molecule expression in acute myeloid leukemia cells. Leukemia. 2004;18:1223–30. doi:10.1038/sj.leu.2403391.
   PubMed Web of Science ®Google Scholar
• Ravandi F, Assi R, Daver N, Benton CB, Kadia T, Thompson PA, Borthakur G, Alvarado Y, Jabbour EJ, Konopleva M, et al. Idarubicin, cytarabine, and nivolumab in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome: a single-arm, phase 2 study. Lancet Haematol. 2019;6:e480–e488. doi:10.1016/S2352-3026(19)30114-0.
   PubMed Web of Science ®Google Scholar
• Saha A, Aoyama K, Taylor PA, Koehn BH, Veenstra RG, Panoskaltsis-Mortari A, Munn DH, Murphy WJ, Azuma M, Yagita H, et al. Host programmed death ligand 1 is dominant over programmed death ligand 2 expression in regulating graft-versus-host disease lethality. Blood. 2013;122:3062–73. doi:10.1182/blood-2013-05-500801.
   PubMed Web of Science ®Google Scholar
• Davids MS; (BCRP), on behalf of the Leukemia & Lymphoma Society Blood Cancer Research Partnership; Kim HT, Costello C, Herrera AF, Locke FL, Maegawa RO, Savell A, Mazzeo M, Anderson A, Boardman AP, et al. A multicenter phase 1 study of nivolumab for relapsed hematologic malignancies after allogeneic transplantation. Blood. 2020;135:2182–91. doi:10.1182/blood.2019004710.
   PubMed Web of Science ®Google Scholar
• Garcia-Manero G, Daver NG, Montalban-Bravo G, Jabbour EJ, DiNardo CD, Kornblau SM, Bose P, Alvarado Y, Ohanian M, Borthakur G, et al. A phase II study evaluating the combination of nivolumab (nivo) or ipilimumab (ipi) with azacitidine in pts with previously treated or untreated myelodysplastic syndromes (MDS). Blood. 2016;128:344–344. doi:10.1182/blood.V128.22.344.344.
   Web of Science ®Google Scholar
• Garcia-Manero G, Sasaki K, Montalban-Bravo G, Daver NG, Jabbour EJ, Alvarado Y, DiNardo CD, Ravandi F, Borthakur G, Bose P, et al. A phase II study of nivolumab or ipilimumab with or without azacitidine for patients with myelodysplastic syndrome (MDS). Blood. 2018;132:465–465.
   PubMed Web of Science ®Google Scholar
• Garcia-Manero G, Montalban-Bravo G, Sasaki K, Daver NG, Jabbour EJ, Alvarado Y, DiNardo CD, Ravandi F, Borthakur G, Bose P, et al. Double immune checkpoint inhibitor blockade with nivolumab and ipilimumab with or without azacitidine in patients with myelodysplastic syndrome (MDS). Blood. 2018;132:1831–1831. doi:10.1182/blood-2018-99-118948.
   Web of Science ®Google Scholar
• Genentech Inc. Atezolizumab prescribing information. FDA; 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761034s018lbl.pdf
   Google Scholar
• Gerds AT, Scott BL, Greenberg PL, Khaled SK, Lin TL, Pollyea DA, Verma A, Dail M, Green C, Ma C, et al. PD-L1 blockade with atezolizumab in higher-risk myelodysplastic syndrome: an initial safety and efficacy analysis. Blood. 2018;132:466–466. doi:10.1182/blood-2018-99-118577.
   Web of Science ®Google Scholar
• O’Connell CL, Kropf PL, Punwani N, Rogers D, Sposto R, Grønbæk K. 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;132:1811–1811.
   Web of Science ®Google Scholar
• Bristol-Myers Squibb Company. Ipilimumab prescribing information. 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/125377s110lbl.pdf
   Google Scholar
• Kokkaliaris KD, Scadden DT. Cell interactions in the bone marrow microenvironment affecting myeloid malignancies. Blood Adv. 2020;4:3795–803. doi:10.1182/bloodadvances.2020002127.
   PubMed Web of Science ®Google Scholar
• Zeidan AM, Knaus H, Robinson TM, Zeidner JF, Blackford AL, Rizzieri D, Frattini MG, Levy MY, Schroeder MA, Ferguson AK, et al. A phase I trial of ipilimumab (ipi) in patients (pts) with myelodysplastic syndromes (MDS) after hypomethylating agent (HMAs) failure. JCO. 2017;35:7010. doi:10.1200/JCO.2017.35.15_suppl.7010.
   Web of Science ®Google Scholar
• Robinson TM, Knaus H, Smith BD, Towlerton AM, Warren EH, Zeidner JF, Blackford A, Duffield AS, Rizzieri D, Frattini MG, et al. Immunological correlates of treatment with the CTLA-4 inhibitor ipilimumab in patients with refractory myelodysplastic syndromes (MDS). Blood. 2017;130:1699–1699. doi:10.1182/blood-2017-04-778225.
   PubMed Web of Science ®Google Scholar
• Banerjee H, Kane LP. Immune regulation by tim-3. F1000Res. 2018;7:316. doi:10.12688/f1000research.13446.1.
   PubMedGoogle Scholar
• Borate U, Esteve J, Porkka K, Knapper S, Vey N, Scholl S, Garcia-Manero G, Wermke M, Janssen J, Traer E, et al. Phase Ib study of the anti-TIM-3 antibody MBG453 in combination with decitabine in patients with high-risk myelodysplastic syndrome (MDS) and Acute Myeloid Leukemia (AML). Blood. 2019;134:570–570. doi:10.1182/blood-2019-128178.
   Web of Science ®Google Scholar
• Borate U, Esteve J, Porkka K. Anti-TIM-3 antibody MBG453 in combination with hypomethylating agents in patients with high-risk myelodysplastic syndrome and acute myeloid leukemia: a phase 1 study. 25th European Hematology Association Congress. 2020.
   Google Scholar
• Sick E, Jeanne A, Schneider C, Dedieu S, Takeda K, Martiny L. CD47 update: a multifaceted actor in the tumour microenvironment of potential therapeutic interest. Br J Pharmacol. 2012;167:1415–30. doi:10.1111/j.1476-5381.2012.02099.x.
   PubMed Web of Science ®Google Scholar
• Chao MP, Takimoto CH, Feng DD, McKenna K, Gip P, Liu J, Volkmer JP, Weissman IL, Majeti R. Therapeutic targeting of the macrophage immune checkpoint CD47 in myeloid malignancies. Front Oncol. 2020;9. doi:10.3389/fonc.2019.01380.
   PubMed Web of Science ®Google Scholar
• Majeti R, Chao MP, Alizadeh AA, Pang WW, Jaiswal S, Gibbs KD, Van Rooijen N, Weissman IL. CD47 is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells. Cell. 2009;138:286–99. doi:10.1016/j.cell.2009.05.045.
   PubMed Web of Science ®Google Scholar
• Boasman K, Simmonds MJ, Rinaldi CR. Expression of CD47 and calr in myeloproliferative neoplasms and myelodysplastic syndrome: potential new therapeutical targets. Blood. 2019;134:5031–5031. doi:10.1182/blood-2019-128422.
   Web of Science ®Google Scholar
• Jaiswal S, Chao MP, Majeti R, Weissman IL. Macrophages as mediators of tumor immunosurveillance. Trends Immunol. 2010;31:212–19.
   PubMed Web of Science ®Google Scholar
• Feng D, Gip P, McKenna KM, Zhao F, Mata O, Choi TS, Duan J, Sompalli K, Majeti R, Weissman IL, et al. Combination treatment with 5F9 and azacitidine enhances phagocytic elimination of acute myeloid leukemia. Blood. 2018;132:2729–2729. doi:10.1182/blood-2018-99-120170.
   Web of Science ®Google Scholar
• Zeidan AM, DeAngelo DJ, Palmer JM, Seet CS, Tallman MS, Wei X, Li YF, Hock N, Burgess MR, Hege K, et al. A phase I study of CC-90002, a monoclonal antibody targeting CD47, in patients with relapsed and/or refractory (R/R) acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS): final results. Blood. 2019;134:1320–1320. doi:10.1182/blood-2019-125363.
   Web of Science ®Google Scholar
• Brierley CK, Staves J, Roberts C, Johnson H, Vyas P, Goodnough LT, Murphy MF. The effects of monoclonal anti-CD47 on RBCs, compatibility testing, and transfusion requirements in refractory acute myeloid leukemia. Transfusion. 2019;59(7):2248–54. doi:10.1111/trf.15397.
   PubMed Web of Science ®Google Scholar
• Chen JY, McKenna KM, Choi TS, Duan J, Brown L, Stewart JJ, Sompalli K, Vyas P, Schrier S, Majeti R, et al. RBC-specific CD47 pruning confers protection and underlies the transient anemia in patients treated with anti-CD47 antibody 5F9. Blood. 2018;132:2327–2327. doi:10.1182/blood-2018-99-115674.
   Web of Science ®Google Scholar
• Kidder K, Bian Z, Shi L, Liu Y. Inflammation unrestrained by SIRPα induces secondary hemophagocytic lymphohistiocytosis independent of IFN-γ. J Immunol. 2020;205:2821–33. doi:10.4049/jimmunol.2000652.
   PubMed Web of Science ®Google Scholar
• Sallman DA, Donnellan WB, Asch AS, Lee DJ, Al Malki M, Marcucci G, Pollyea DA, Kambhampati S, Komrokji RS, Van Elk J, et al. The first-in-class anti-CD47 antibody Hu5F9-G4 is active and well tolerated alone or with azacitidine in AML and MDS patients: initial phase 1b results. JCO. 2019;37:7009. doi:10.1200/JCO.2019.37.15_suppl.7009.
   Google Scholar
• Sallman DA, Asch AS, Al Malki MM, Lee DJ, Donnellan WB, Marcucci G, Kambhampati S, Daver NG, Garcia-Manero G, Komrokji RS, 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;134:569–569. doi:10.1182/blood-2019-126271.
   Web of Science ®Google Scholar
• Sallman DA, Al Malki M, Asch AS, Lee DJ, Kambhampati S, Donnellan WB, Bradley TJ, Vyas P, Jeyakumar D, Marcucci G, et al. Tolerability and efficacy of the first-in-class anti-CD47 antibody magrolimab combined with azacitidine in MDS and AML patients: phase ib results. JCO. 2020;38:7507. doi:10.1200/JCO.2020.38.15_suppl.7507.
   Web of Science ®Google Scholar
• Lonez C, Verma B, Hendlisz A, Aftimos P, Awada A, Van Den Neste E, Catala G, Machiels JP, Piette F, Brayer JB, et al. Study protocol for THINK: a multinational open-label phase I study to assess the safety and clinical activity of multiple administrations of NKR-2 in patients with different metastatic tumour types. BMJ Open. 2017;7:e017075. doi:10.1136/bmjopen-2017-017075.
   PubMed Web of Science ®Google Scholar
• Houchins JP, Yabe T, McSherry C, Miyokawa N, Bach FH. Isolation and characterization of NK cell or NK/T cell-specific cDNA clones. J Mole Cell Immunol. 1990;4:295–304. discussion 305.
   PubMedGoogle Scholar
• Carapito R, Bahram S. Genetics, genomics, and evolutionary biology of NKG2D ligands. Immunol Rev. 2015;267:88–116.
   PubMed Web of Science ®Google Scholar
• Murad JM, Baumeister SH, Werner L, Daley H, Trébéden-Negre H, Reder J, Sentman CL, Gilham D, Lehmann F, Snykers S, et al. Manufacturing development and clinical production of NKG2D chimeric antigen receptor-expressing T cells for autologous adoptive cell therapy. Cytotherapy. 2018;20:952–63. doi:10.1016/j.jcyt.2018.05.001.
   PubMed Web of Science ®Google Scholar
• Spear P, Wu M, Sentman M, Sentman CL. NKG2D ligands as therapeutic targets. Cancer Immun. 2013;13:8.
   PubMedGoogle Scholar
• Giuliani M, Poggi A. Checkpoint inhibitors and engineered cells: new weapons for natural killer cell arsenal against hematological malignancies. Cells. 2020;9:1578. doi:10.3390/cells9071578.
   PubMed Web of Science ®Google Scholar
• Zhang T, Barber A, Sentman CL. Generation of antitumor responses by genetic modification of primary human T cells with a chimeric NKG2D receptor. Cancer Res. 2006;66:5927–33. doi:10.1158/0008-5472.CAN-06-0130.
   PubMed Web of Science ®Google Scholar
• Barber A, Meehan KR, Sentman CL. Treatment of multiple myeloma with adoptively transferred chimeric NKG2D receptor-expressing T cells. Gene Ther. 2011;18:509–16. doi:10.1038/gt.2010.174.
   PubMed Web of Science ®Google Scholar
• Gilfillan S, Ho EL, Cella M, Yokoyama WM, Colonna M. NKG2D recruits two distinct adapters to trigger NK cell activation and costimulation. Nat Immunol. 2002;3:1150–55. doi:10.1038/ni857.
   PubMed Web of Science ®Google Scholar
• Baumeister SH, Murad J, Werner L, Daley H, Trebeden-Negre H, Gicobi JK, Schmucker A, Reder J, Sentman CL, Gilham DE, et al. Phase I trial of autologous CAR T cells targeting NKG2D ligands in patients with AML/MDS and multiple myeloma. Cancer Immunol Res. 2019;7:100–12. doi:10.1158/2326-6066.CIR-18-0307.
   PubMed Web of Science ®Google Scholar
• Bert NL, Gasser S. Advances in NKG2D ligand recognition and responses by NK cells. Immunol Cell Biol. 2014;92:230–36. doi:10.1038/icb.2013.111.
   PubMed Web of Science ®Google Scholar
• Nikiforow S, Werner L, Murad J, Jacobs M, Johnston L, Patches S, White R, Daley H, Negre H, Reder J, et al. Safety data from a first-in-human phase 1 trial of NKG2D chimeric antigen receptor-T cells in AML/MDS and multiple Myeloma. Blood. 2016;128:4052–4052. doi:10.1182/blood.V128.22.4052.4052.
   Google Scholar
• Anonymous Pioneering innovative therapies for patients with life-threatening diseases. ASH 2019 Presentation Update on r/r AML and MDS Program; 2019 Dec 9 [accessed Nov 27]. https://celyad.com/wp-content/uploads/2020/08/Celyad-ASH-Symposium-Presentation_December-9_vF.pdf
   Google Scholar
• Sallman DA, Brayer JB, Poire X, Havelange V, Awada A, Lewalle P, Odunsi K, Wang ES, Lonez C, Lequertier T, et al. Results from the completed dose-escalation of the hematological arm of the phase I think study evaluating multiple infusions of NKG2D-based CAR T-cells as standalone therapy in relapse/refractory acute myeloid leukemia and myelodysplastic syndrome patients. Blood. 2019;134:3826–3826. doi:10.1182/blood-2019-128020.
   Web of Science ®Google Scholar
• Liu H, Wang S, Xin J, Wang J, Yao C, Zhang Z. Role of NKG2D and its ligands in cancer immunotherapy. Am J Cancer Res. 2019;9:2064–78.
   PubMed Web of Science ®Google Scholar
• Gasser S, Orsulic S, Brown EJ, Raulet DH. The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor. Nature (London). 2005;436:1186–90. doi:10.1038/nature03884.
   PubMed Web of Science ®Google Scholar
• Al-Homsi AS, Purev E, Lewalle P, Abdul-Hay M, Pollyea DA, Salaroli A, Lequertier T, Alcantar-Orozco E, Borghese F, Lonez C, et al. Interim results from the phase I deplethink trial evaluating the infusion of a NKG2D CAR T-cell therapy post a non-myeloablative conditioning in relapse or refractory acute myeloid leukemia and myelodysplastic syndrome patients. Blood. 2019;134:3844–3844. doi:10.1182/blood-2019-128267.
   Web of Science ®Google Scholar
• Hong S, Rybicki L, Corrigan D, Hamilton BK, Sobecks R, Kalaycio M, Dean RM, Hill BT, Pohlman B, Jagadeesh D, et al. Targeted treatment and survival following relapse after allogeneic hematopoietic cell transplantation for acute leukemia and MDS in the contemporary era. Blood. 2019;134:4567–4567. doi:10.1182/blood-2019-124533.
   Google Scholar
• Krishnamurthy P, Potter VT, Barber LD, Kulasekararaj AG, Lim ZY, Pearce RM, De Lavallade H, Kenyon M, Ireland RM, Marsh JCW, et al. Outcome of donor lymphocyte infusion after T cell-depleted allogeneic hematopoietic stem cell transplantation for acute myelogenous leukemia and myelodysplastic syndromes. Biol Blood Marrow Transplant. 2013;19:562–68. doi:10.1016/j.bbmt.2012.12.013.
   PubMed Web of Science ®Google Scholar
• Claiborne J, Bandyopathyay D, Roberts C, Hawks K, Aziz M, Simmons G, Wiedl C, Chung H, Clark W, McCarty J, et al. Managing post allograft relapse of myeloid neoplasms: azacitidine and donor lymphocyte infusions as salvage therapy. Leuk Lymphoma. 2019;60:2733–43. doi:10.1080/10428194.2019.1605066.
   PubMed Web of Science ®Google Scholar
• Zeiser R, Beelen DW, Bethge W, Bornhäuser M, Bug G, Burchert A, Christopeit M, Duyster J, Finke J, Gerbitz A, et al. Biology-driven approaches to prevent and treat relapse of myeloid neoplasia after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2019;25:e128–e140. doi:10.1016/j.bbmt.2019.01.016.
   PubMedGoogle Scholar
• Lulla P, Naik S, Tzannou I, Mukhi S, Kuvalekar M, Robertson C, Ramos CA, Carrum G, Kamble RT, Gee AP, et al. Administering leukemia-directed donor lymphocytes to patients with AML or MDS to prevent or treat post-allogeneic HSCT relapse. Biol Blood Marrow Transplant. 2019;25:S10–S11. doi:10.1016/j.bbmt.2018.12.075.
   Google Scholar
• Epperly R, Gottschalk S, Velasquez MP. A bump in the road: how the hostile AML microenvironment affects CAR T cell therapy. Front Oncol. 2020;10:262. doi:10.3389/fonc.2020.00262.
   PubMed Web of Science ®Google Scholar
• Sarhan D, Wang J, Sunil Arvindam U, Hallstrom C, Verneris MR, Grzywacz B, Warlick E, Blazar BR, Miller JS. Mesenchymal stromal cells shape the MDS microenvironment by inducing suppressive monocytes that dampen NK cell function. JCI Insight. 2020;5:5. doi:10.1172/jci.insight.130155.
   Web of Science ®Google Scholar
• Bergmann L, Maurer U, Weidmann E. Wilms tumor gene expression in acute myeloid leukemias. Leuk Lymphoma. 1997;25:435–43. doi:10.3109/10428199709039030.
   PubMed Web of Science ®Google Scholar
• Cilloni D, Gottardi E, Messa F, Fava M, Scaravaglio P, Bertini M, Girotto M, Marinone C, Ferrero D, Gallamini A, et al. Significant correlation between the degree of WT1 expression and the international prognostic scoring system score in patients with myelodysplastic syndromes. JCO. 2003;21:1988–95. doi:10.1200/JCO.2003.10.503.
   PubMed Web of Science ®Google Scholar
• Rautenberg C, Germing U, Pechtel S, Lamers M, Fischermanns C, Jäger P, Geyh S, Haas R, Kobbe G, Schroeder T, et al. Prognostic impact of peripheral blood WT1- mRNA expression in patients with MDS. Blood Cancer J. 2019;9:1–8. doi:10.1038/s41408-019-0248-y.
   Web of Science ®Google Scholar
• Jo T, Sakai K, Muranushi H, Okamoto Y, Tsukamoto T, Sugiura H, Matsui H, Ueda T, Okada K, Maeda T, et al. Pre-treatment WT1 mRNA expression level in peripheral blood predicts response and overall survival of myelodysplastic syndrome patients in the azacitidine era. Blood. 2013;122:1528–1528. doi:10.1182/blood.V122.21.1528.1528.
   Web of Science ®Google Scholar
• Gao L, Bellantuono I, Elsasser A, Marley SB, Gordon MY, Goldman JM, Stauss HJ. Selective elimination of leukemic CD34+ progenitor cells by cytotoxic T lymphocytes specific for WT1. Blood. 2000;95:2198–203. doi:10.1182/blood.V95.7.2198.
   PubMed Web of Science ®Google Scholar
• Pinilla-Ibarz J, May RJ, Korontsvit T, Gomez M, Kappel B, Zakhaleva V, Zhang RH, Scheinberg DA. Improved human T-cell responses against synthetic HLA-0201 analog peptides derived from the WT1 oncoprotein. Leukemia. 2006;20:2025–33. doi:10.1038/sj.leu.2404380.
   PubMed Web of Science ®Google Scholar
• Ohminami H, Yasukawa M, Fujita S. HLA class I-restricted lysis of leukemia cells by a CD8(+) cytotoxic T-lymphocyte clone specific for WT1 peptide. Blood. 2000;95:286–93. doi:10.1182/blood.V95.1.286.
   PubMed Web of Science ®Google Scholar
• Rezvani K, Yong ASM, Mielke S, Jafarpour B, Savani BN, Le RQ, Eniafe R, Musse L, Boss C, Kurlander R, et al. Repeated PR1 and WT1 peptide vaccination in montanide-adjuvant fails to induce sustained high-avidity, epitope-specific CD8+ T cells in myeloid malignancies. Haematologica. 2011;96:432–40. doi:10.3324/haematol.2010.031674.
   PubMed Web of Science ®Google Scholar
• Rezvani K, Yong ASM, Mielke S, Savani BN, Musse L, Superata J, Jafarpour B, Boss C, Barrett AJ. Leukemia-associated antigen-specific T-cell responses following combined PR1 and WT1 peptide vaccination in patients with myeloid malignancies. Blood. 2008;111:236–42. doi:10.1182/blood-2007-08-108241.
   PubMed Web of Science ®Google Scholar
• Brayer J, Lancet JE, Powers J, List A, Balducci L, Komrokji R, Pinilla-Ibarz J. WT1 vaccination in AML and MDS: a pilot trial with synthetic analog peptides. Am J Hematol. 2015;90:602–07. doi:10.1002/ajh.24014.
   PubMed Web of Science ®Google Scholar
• Suzuki T, Ueda Y, Ogura M, Uchida T, Ozawa K, Miyakoshi S, Naoe T, Murata M, Kizaki M, Uike N, et al. A phase 1/2 study of WT1 peptide cancer vaccine WT4869 in patients with myelodysplastic syndromes (MDS). Blood. 2015;126:2868–2868. doi:10.1182/blood.V126.23.2868.2868.
   Google Scholar
• Keilholz U, Letsch A, Busse A, Asemissen AM, Bauer S, Blau IW, Hofmann WK, Uharek L, Thiel E, Scheibenbogen C, et al. A clinical and immunologic phase 2 trial of wilms tumor gene product 1 (WT1) peptide vaccination in patients with AML and MDS. Blood. 2009;113:6541–48. doi:10.1182/blood-2009-02-202598.
   PubMed Web of Science ®Google Scholar
• Molldrem J, Dermime S, Parker K, Jiang YZ, Mavroudis D, Hensel N, Fukushima P, Barrett AJ. Targeted T-cell therapy for human leukemia: cytotoxic T lymphocytes specific for a peptide derived from proteinase 3 preferentially lyse human myeloid leukemia cells. Blood. 1996;88:2450–57. doi:10.1182/blood.V88.7.2450.bloodjournal8872450.
   PubMed Web of Science ®Google Scholar
• Molldrem JJ, Lee PP, Kant S, Wieder E, Jiang W, Lu S, Wang C, Davis MM. Chronic myelogenous leukemia shapes host immunity by selective deletion of high-avidity leukemia-specific T cells. J Clin Invest. 2003;111:639–47. doi:10.1172/JCI200316398.
   PubMed Web of Science ®Google Scholar
• Qazilbash MH, Wieder E, Thall PF, Wang X, Rios R, Lu S, Kanodia S, Ruisaard KE, Giralt SA, Estey EH, et al. PR1 peptide vaccine induces specific immunity with clinical responses in myeloid malignancies. Leukemia. 2017;31:697–704. doi:10.1038/leu.2016.254.
   PubMed Web of Science ®Google Scholar
• Almstedt M, Blagitko-Dorfs N, Duque-Afonso J, Karbach J, Pfeifer D, Jäger E, Lübbert M. The DNA demethylating agent 5-aza-2ʹ-deoxycytidine induces expression of NY-ESO-1 and other cancer/testis antigens in myeloid leukemia cells. Leuk Res. 2010;34:899–905. doi:10.1016/j.leukres.2010.02.004.
   PubMed Web of Science ®Google Scholar
• Satie A, Meyts ER, Spagnoli GC, Henno S, Olivo L, Jacobsen GK, Rioux-Leclercq N, Jégou B, Samson M. The cancer-testis gene, NY-ESO-1, is expressed in normal fetal and adult testes and in spermatocytic seminomas and testicular carcinoma. Lab Invest. 2002;82:775–80. doi:10.1097/01.LAB.0000017169.26718.5F.
   PubMed Web of Science ®Google Scholar
• Zendman AJW, Ruiter DJ, Van Muijen GNP. Cancer/testis-associated genes: identification, expression profile, and putative function. J Cell Physiol. 2003;194:272–88. doi:10.1002/jcp.10215.
   PubMed Web of Science ®Google Scholar
• Scanlan MJ, Simpson AJG, Old LJ. The cancer/testis genes: review, standardization, and commentary. Cancer Immun. 2004;4:1.
   PubMedGoogle Scholar
• Thomas R, Al-Khadairi G, Roelands J, Hendrickx W, Dermime S, Bedognetti D, Decock J. NY-ESO-1 based immunotherapy of cancer: current perspectives. Front Immunol. 2018;9:947. doi:10.3389/fimmu.2018.00947.
   PubMed Web of Science ®Google Scholar
• De Smet C, De Backer O, Faraoni I, Lurquin C, Brasseur F, Boon T. The activation of human gene MAGE-1 in tumor cells is correlated with genome-wide demethylation. Proc Natl Acad Sci USA. 1996;93:7149–53. doi:10.1073/pnas.93.14.7149.
   PubMed Web of Science ®Google Scholar
• Atanackovic D, Luetkens T, Kloth B, Fuchs G, Cao Y, Hildebrandt Y, Meyer S, Bartels K, Reinhard H, Lajmi N, et al. Cancer-testis antigen expression and its epigenetic modulation in acute myeloid leukemia. Am J Hematol. 2011;86:918–22. doi:10.1002/ajh.22141.
   PubMed Web of Science ®Google Scholar
• Srivastava P, Paluch BE, Matsuzaki J, James SR, Collamat-Lai G, Blagitko-Dorfs N, Ford LA, Naqash R, Lübbert M, Karpf AR, et al. Induction of cancer testis antigen expression in circulating acute myeloid leukemia blasts following hypomethylating agent monotherapy. Oncotarget. 2016;7:12840–56. doi:10.18632/oncotarget.7326.
   PubMed Web of Science ®Google Scholar
• Griffiths EA, Srivastava P, Matsuzaki J, Brumberger Z, Wang ES, Kocent J, Miller A, Roloff GW, Wong HY, Paluch BE, et al. NY-ESO-1 vaccination in combination with decitabine induces antigen-specific T-lymphocyte responses in patients with myelodysplastic syndrome. Clin Cancer Res. 2018;24:1019–29. doi:10.1158/1078-0432.CCR-17-1792.
   PubMed Web of Science ®Google Scholar
• Steger B, Floro L, Amberger DC, Kroell T, Tischer J, Kolb H-J, Schmetzer HM. WT1, PRAME, and PR3 mRNA expression in acute myeloid leukemia (AML). J Immunother. 2020;43:204–15. doi:10.1097/CJI.0000000000000322.
   PubMed Web of Science ®Google Scholar
• Borrello I, Sotomayor EM, Cooke S, Levitsky HI. A universal granulocyte-macrophage colony-stimulating factor-producing bystander cell line for use in the formulation of autologous tumor cell-based vaccines. Hum Gene Ther. 1999;10:1983–91. doi:10.1089/10430349950017347.
   PubMed Web of Science ®Google Scholar
• Lozzio CB, Lozzio BB. Human chronic myelogenous leukemia cell-line with positive philadelphia chromosome. Blood. 1975;45:321–34. doi:10.1182/blood.V45.3.321.321.
   PubMed Web of Science ®Google Scholar
• Smith BD, Kasamon YL, Kowalski J, Gocke C, Murphy K, Miller CB, Garrett-Mayer E, Tsai H-L, Qin L, Chia C, et al. K562/GM-CSF immunotherapy reduces tumor burden in chronic myeloid leukemia patients with residual disease on imatinib mesylate. Clin Cancer Res. 2010;16:338–47. doi:10.1158/1078-0432.CCR-09-2046.
   PubMed Web of Science ®Google Scholar
• Robinson TM, Prince GT, Thoburn C, Warlick E, Ferguson A, Kasamon YL, Borrello IM, Hess A, Smith BD. Pilot trial of K562/GM-CSF whole-cell vaccination in MDS patients. Leuk Lymphoma. 2018;59:2801–11. doi:10.1080/10428194.2018.1443449.
   PubMed Web of Science ®Google Scholar
• Saft L, Björklund E, Berg E, Hellström-Lindberg E, Porwit A. Bone marrow dendritic cells are reduced in patients with high-risk myelodysplastic syndromes. Leuk Res. 2013;37:266–73. doi:10.1016/j.leukres.2012.10.010.
   PubMedGoogle Scholar