Immunotherapy of elderly acute myeloid leukemia: light at the end of a long tunnel?

References

• Pulte D, Gondos A, Brenner H. Expected long-term survival of patients diagnosed with acute myeloblastic leukemia during 2006–2010. Ann Oncol. 2010;21:335–341.
   PubMed Web of Science ®Google Scholar
• Appelbaum FR, Gundacker H, Head DR, et al. Age and acute myeloid leukemia. Blood. 2006;107:3481–3485.
   PubMed Web of Science ®Google Scholar
• Rashidi A, Ebadi M, Colditz GA, et al. Outcomes of allogeneic stem cell transplantation in elderly patients with acute myeloid leukemia: a systematic review and meta-analysis. Biol Blood Marrow Transplant. 2016;22:651–657.
   PubMed Web of Science ®Google Scholar
• Löwenberg B, Ossenkoppele GJ, van Putten W, et al. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med. 2009;361:1235–1248.
   PubMed Web of Science ®Google Scholar
• Sullivan KM, Weiden PL, Storb R, et al. Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia. Blood. 1989;73:1720–1728.
   PubMed Web of Science ®Google Scholar
• Schmid C, Labopin M, Nagler A, et al. Donor lymphocyte infusion in the treatment of first hematological relapse after allogeneic stem-cell transplantation in adults with acute myeloid leukemia: a retrospective risk factors analysis and comparison with other strategies by the EBMT Acute Leukemia Working Party. J Clin Oncol. 2007;25:4938–4945.
   PubMed Web of Science ®Google Scholar
• Mutis T, Verdijk R, Schrama E, et al. Feasibility of immunotherapy of relapsed leukemia with ex vivo-generated cytotoxic T lymphocytes specific for hematopoietic system-restricted minor histocompatibility antigens. Blood. 1999;93:2336–2341.
   PubMed Web of Science ®Google Scholar
• Gambacorti-Passerini C, Grignani F, Arienti F, et al. Human CD4 lymphocytes specifically recognize a peptide representing the fusion region of the hybrid protein PML/RAR alpha present in acute promyelocytic leukemia cells. Blood. 1993;81:1369–1375.
   PubMed Web of Science ®Google Scholar
• Rizvi NA, Hellmann MD, Synder A, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348:124–128.
   PubMed Web of Science ®Google Scholar
• McGranahan N, Furness A, Rosenthal R, et al. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science. 2016;351:1463–1469.
   PubMed Web of Science ®Google Scholar
• Asemissen AM, Keilholz U, Tenzer S, et al. Identification of a highly immunogenic HLA-A*01-binding T cell epitope of WT1. Clin Cancer Res. 2006;12:7476–7482.
   PubMed Web of Science ®Google Scholar
• Scheibenbogen C, Letsch A, Thiel E, et al. CD8 T-cell responses to Wilms tumor gene product WT1 and proteinase 3 in patients with acute myeloid leukemia. Blood. 2002;100:2132–2137.
   PubMed Web of Science ®Google Scholar
• Adotévi O, Mollier K, Neuveut C, et al. Immunogenic HLA-B* 0702-restricted epitopes derived from human telomerase reverse transcriptase that elicit antitumor cytotoxic T-cell responses. Clin Cancer Res. 2006;12:3158–3167.
   PubMed Web of Science ®Google Scholar
• Vonderheide RH, Hahn WC, Schultze JL, et al. The telomerase catalytic subunit is a widely expressed tumor-associated antigen recognized by cytotoxic T lymphocytes. Immunity.1999;10:673–679.
   PubMed Web of Science ®Google Scholar
• Martínez A, Olarte I, Mergold MA, et al. mRNA expression of MAGE-A3 gene in leukemia cells. Leuk Res. 2007;31:33–37.
   PubMed Web of Science ®Google Scholar
• Goodyear O, Agathanggelou A, Novitzky-Basso I, et al. Induction of a CD8+ T-cell response to the MAGE cancer testis antigen by combined treatment with azacitidine and sodium valproate in patients with acute myeloid leukemia and myelodysplasia. Blood. 2010;116:1908–1918.
   PubMed Web of Science ®Google Scholar
• Atanackovic D, Luetkens T, Kloth B, et al. Cancer-testis antigen expression and its epigenetic modulation in acute myeloid leukemia. Am J Hematol. 2011;86:918–922.
   PubMed Web of Science ®Google Scholar
• van Baren N, Chambost H, Ferrant A, et al. PRAME, a gene encoding an antigen recognized on a human melanoma by cytolytic T cells, is expressed in acute leukaemia cells. Brit J Haematol. 1998;102:1376–1379.
   PubMed Web of Science ®Google Scholar
• Wang Z, Zhang Y, Mandal A, et al. The spermatozoa protein, SLLP1, is a novel cancer–testis antigen in hematologic malignancies. Clin Cancer Res. 2004;10:6544–6550.
   PubMed Web of Science ®Google Scholar
• Li Z, Li W, Meklat F, et al. A yeast two-hybrid system using Sp17 identified Ropporin as a novel cancer-testis antigen in hematologic malignancies. Int J Cancer. 2007;121:1507–1511.
   PubMed Web of Science ®Google Scholar
• Lim SH, Austin S, Owen-Jones E, et al. Expression of testicular genes in haematological malignancies. Br J Cancer. 1999;81:1162–1164.
   PubMed Web of Science ®Google Scholar
• Wang Z, Zhang Y, Liu H, et al. Gene expression and immunologic consequence of SPAN-Xb in myeloma and other hematologic malignancies. Blood. 2003;101:955–960.
   PubMed Web of Science ®Google Scholar
• Bonnet D, Warren EH, Greenberg PD, et al. CD8+ minor histocompatibility antigen-specific cytotoxic T lymphocyte clones eliminate human acute myeloid leukemia stem cells. Proc Natl Acad Sci. 1999;96:8639–8644.
   PubMed Web of Science ®Google Scholar
• Falkenburg JH, Goselink HM, van der Harst D, et al. Growth inhibition of clonogenic leukemic precursor cells by minor histocompatibility antigen-specific cytotoxic T lymphocytes. J Exp Med. 1991;174:27–33.
   PubMed Web of Science ®Google Scholar
• Tsukada N, Aoki S, Maruyama S, et al. The heterogeneous expression of CD80, CD86 and other adhesion molecules on leukemia and lymphoma cells and their induction by interferon. J Exp Clin Cancer Res. 1997;16:171–176.
   PubMed Web of Science ®Google Scholar
• Powles RL, Crowther D, Bateman CJ, et al. Immunotherapy for acute myelogenous leukaemia. Br J Cancer. 1973;28:365–376.
   PubMed Web of Science ®Google Scholar
• Summerfield GP, Gibbs TJ, Bellingham AJ. Immunotherapy using BCG during remission induction and as the sole form of maintenance in acute myeloid leukaemia. Br J Cancer. 1979;40:736–742.
   PubMed Web of Science ®Google Scholar
• McCredie KB, Gehan EA, Freireich EJ, et al. Management of adult acute leukemia a Southwest Oncology Group Study. Cancer. 1983;52:958–966.
   PubMed Web of Science ®Google Scholar
• Foon KA, Smalley RV, Riggs CW, et al. The role of immunotherapy in acute myelogenous leukemia. Arch Intern Med. 1983;143:1726–1731.
   PubMed Web of Science ®Google Scholar
• Rohatiner AZ, Balkwill FR, Griffin DB, et al. A phase I study of human lymphoblastoid interferon administered by continuous intravenous infusion. Cancer Chemother Pharm. 1982;9:97–102.
   PubMed Web of Science ®Google Scholar
• Lim SH, Marcus RE, Baglin TP. A pilot study of low dose ARA-C, Interferon-alpha and cis-retinoic acid (AIR) combination therapy for poor prognosis acute myeloid leukaemia Leuk Lymphoma. 1991;5:341–345.
   PubMed Web of Science ®Google Scholar
• Bezwoda WR, Seymour L, Ruff P. Combined cytosine arabinoside plus Interferon alpha: II. Clinical studies in leukemia and lymphoma. Int J Oncol. 1993;2:469–469.
   PubMed Web of Science ®Google Scholar
• Goldstone AH, Burnett AK, Wheatley K, et al. Attempts to improve treatment outcomes in acute myeloid leukemia (AML) in older patients: the results of the United Kingdom Medical Research Council AML11 trial. Blood. 2001;98:1302–1311.
   PubMed Web of Science ®Google Scholar
• Lim SH, Newland AC, Kelsey S, et al. Continuous intravenous infusion of high-dose recombinant interleukin-2 for acute myeloid leukaemia - a phase II study. Cancer Immunol Immunother. 1992;34:337–342.
   PubMed Web of Science ®Google Scholar
• Maraninchi D, Blaise D, Viens P, et al. High-dose recombinant interleukin-2 and acute myeloid leukemias in relapse. Blood. 1991;78:2182–2187.
   PubMed Web of Science ®Google Scholar
• Meloni G, Foa R, Vignetti M, et al. Interleukin-2 may induce prolonged remissions in advanced acute myelogenous leukemia. Blood. 1994;84:2158–2163.
   PubMed Web of Science ®Google Scholar
• Hamon MD, Prentice HG, Gottlieb DJ, et al. Immunotherapy with interleukin 2 after ABMT in AML. Bone Marrow Transplant. 1993;11:399–401.
   PubMed Web of Science ®Google Scholar
• Benyunes MC, Massumoto C, York A, et al. Interleukin-2 with or without lymphokine-activated killer cells as consolidative immunotherapy after autologous bone marrow transplantation for acute myelogenous leukemia. Bone Marrow Transplant. 1993;12:159–163.
   PubMed Web of Science ®Google Scholar
• Lopez-Girona A, Mendy D, Ito T, et al. Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide. Leukemia. 2010;26:2326–2335.
   Web of Science ®Google Scholar
• Fehniger TA, Byrd JC, Marcucci G, et al. Single-agent lenalidomide induces complete remission of acute myeloid leukemia in patients with isolated trisomy 13. Blood. 2009;113:1002–1005.
   PubMed Web of Science ®Google Scholar
• Blum W, Klisovic RB, Becker H, et al. Dose escalation of lenalidomide in relapsed or refractory acute leukemias. J Clin Oncol. 2010;28:4919–4925.
   PubMed Web of Science ®Google Scholar
• Fehniger TA, Uy GL, Trinkaus K, et al. A phase 2 study of high-dose lenalidomide as initial therapy for older patients with acute myeloid leukemia. Blood. 2011;117:1828–1833.
   PubMed Web of Science ®Google Scholar
• Sekeres MA, Gundacker H, Lancet J, et al. A phase 2 study of lenalidomide monotherapy in patients with deletion 5q acute myeloid leukemia: Southwest Oncology Group Study S0605. Blood. 2011;118:523–528.
   PubMed Web of Science ®Google Scholar
• Pollyea DA, Kohrt HE, Gallegos L, et al. Safety, efficacy and biological predictors of response to sequential azacitidine and lenalidomide for elderly patients with acute myeloid leukemia. Leukemia. 2012;26:893–901.
   PubMed Web of Science ®Google Scholar
• Ramsingh G, Westervelt P, Cashen AF, et al. A phase 1 study of concomitant high-dose lenalidomide and 5-azacitidine induction in the treatment of AML. Leukemia. 2013;27:725–728.
   PubMed Web of Science ®Google Scholar
• Tamura K, Hazama S, Yamaguchi R, et al. Characterization of the T cell repertoire by deep T cell receptor sequencing in tissues and blood from patients with advanced colorectal cancer. Oncol Lett. 2016;11:3643–3649.
   PubMed Web of Science ®Google Scholar
• Priebe T, Platsoucas CD, Seki H, et al. Purine nucleoside modulation of functions of human lymphocytes. Cell Immunol. 1990;129:321–328.
   PubMed Web of Science ®Google Scholar
• Lanier LL, O'Fallon S, Somoza C, et al. CD80 (B7) and CD86 (B70) provide similar costimulatory signals for T cell proliferation, cytokine production, and generation of CTL. J Immunol. 1995;154:97–105.
   PubMed Web of Science ®Google Scholar
• Brouwer RE, van der Heiden P, Schreuder GM, et al. Loss or downregulation of HLA class I expression at the allelic level in acute leukemia is infrequent but functionally relevant, and can be restored by interferon. Hum Immunol. 2002;63:200–210.
   PubMed Web of Science ®Google Scholar
• Vago L, Perna SK, Zanussi M, et al. Loss of mismatched HLA in leukemia after stem-cell transplantation. N Engl J Med. 2009;361:478–488.
   PubMed Web of Science ®Google Scholar
• Berthon C, Driss V, Liu J, et al. In acute myeloid leukemia, B7-H1 (PD-L1) protection of blasts from cytotoxic T cells is induced by TLR ligands and interferon-gamma and can be reversed using MEK inhibitors. Cancer Immunol Immunother. 2010;59:1839–1849.
   PubMed Web of Science ®Google Scholar
• Krönig H, Kremmler L, Haller B, et al. Interferon‐induced programmed death‐ligand 1 (PD‐L1/B7‐H1) expression increases on human acute myeloid leukemia blast cells during treatment. Eur J. Haematol. 2014;92:195–203.
   PubMed Web of Science ®Google Scholar
• Reagan JL, Fast LD, Nevola M, et al. Nonengraftment donor lymphocyte infusions for refractory acute myeloid leukemia. Blood Cancer J. 2015;5:e371.
   PubMed Web of Science ®Google Scholar
• Zhang L, Gajewski TF, Kline J. PD-1/PD-L1 interactions inhibit antitumor immune responses in a murine acute myeloid leukemia model. Blood. 2009;114:1545–1552.
   PubMed Web of Science ®Google Scholar
• Zhou Q, Munger ME, Highfill SL, et al. Program death-1 signaling and regulatory T cells collaborate to resist the function of adoptively transferred cytotoxic T lymphocytes in advanced acute myeloid leukemia. Blood. 2010;116:2484–2493.
   PubMed Web of Science ®Google Scholar
• Albring JC, Inselmann S, Sauer T, et al. PD-1 checkpoint blockade in patients with relapsed AML after allogeneic stem cell transplantation. Bone Marrow Transplant. 2017;52:317?320.
   PubMed Web of Science ®Google Scholar
• Garcia-Manero G, Daver NG, Montalban-Bravo 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;22:S344.
   Google Scholar
• Garcia-Manero G, Tallman MS, Martinelli G, et al. Pembrolizumab, a PD-1 inhibitor, in patients with myelodysplastic syndrome (MDS) after failure of hypomethylating agent treatment. Blood. 2016;22:S345.
   Google Scholar
• Szczepanski MJ, Szajnik M, Czystowska M, et al. Increased frequency and suppression by regulatory T cells in patients with acute myelogenous leukemia. Clin Cancer Res. 2009;15:3325–3332.
   PubMed Web of Science ®Google Scholar
• Zhou Q, Munger ME, Veenstra RG, et al. Coexpression of Tim-3 and PD-1 identifies a CD8+ T-cell exhaustion phenotype in mice with disseminated acute myelogenous leukemia. Blood. 2011;117:4501–4510.
   PubMed Web of Science ®Google Scholar
• Lim SH, Worman CP, Jewell A, et al. Production of tumour-derived suppressor factor in patients with acute myeloid leukaemia. Leuk Res. 1991;15:263–268.
   PubMed Web of Science ®Google Scholar
• Bergmann L, Schui DK, Brieger J, et al. The inhibition of lymphokine-activated killer cells in acute myeloblastic leukemia is mediated by transforming growth factor-beta 1. Exp Hematol. 1995;23:1574–1580.
   PubMed Web of Science ®Google Scholar
• Maurillo L, Venditti A, Spagnoli A, et al. Azacitidine for the treatment of patients with acute myeloid leukemia: report of 82 patients enrolled in an Italian Compassionate Program. Cancer. 2012;118:1014–1022.
   PubMed Web of Science ®Google Scholar
• Fozza C, Corda G, Barraqueddu F, et al. Azacytidine improves the T-cell repertoire in patients with myelodysplastic syndromes and acute myeloid leukemia with multilineage dysplasia. Leuk Res. 2015;39:957–963.
   PubMed Web of Science ®Google Scholar
• Khan R, Schmidt-Mende J, Karimi M, et al. Hypomethylation and apoptosis in 5-azacytidine-treated myeloid cells. Exp Hematol. 2008;36:149–157.
   PubMed Web of Science ®Google Scholar
• Markowicz S, Engleman EG. Granulocyte-macrophage colony-stimulating factor promotes differentiation and survival of human peripheral blood dendritic cells in vitro. J Clin Invest. 1990;85:955–961.
   PubMed Web of Science ®Google Scholar
• Caux C, Vanbervliet B, Massacrier C, et al. CD34+ hematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to GM-CSF + TNF alpha." J Exp Med. 1996;184:695–706.
   PubMed Web of Science ®Google Scholar
• Ahlers JD, Dunlop N, Alling DW, et al. Cytokine-in-adjuvant steering of the immune response phenotype to HIV-1 vaccine constructs: granulocyte-macrophage colony-stimulating factor and TNF-alpha synergize with IL-12 to enhance induction of cytotoxic T lymphocytes. J Immunol. 1997;158:3947–3958.
   PubMed Web of Science ®Google Scholar
• Griffin JD, Young D, Herrmann F, et al. Effects of recombinant human GM-CSF on proliferation of clonogenic cells in acute myeloblastic leukemia. Blood. 1986;67:1448–1453.
   PubMed Web of Science ®Google Scholar
• Gattringer C, Thaler J, Drach J, et al. GM-CSF treatment in aplasia after cytotoxic therapy. Onkologie. 1989;12:16–18.
   PubMedGoogle Scholar
• Buechner T, Hiddemann W, Koenigsmann M, et al. Recombinant human GM-CSF following chemotherapy in high-risk AML. Bone Marrow Transplant. 1990 6:131–134.
   PubMed Web of Science ®Google Scholar
• Estey EH, Dixon D, Kantarjian HM, et al. Treatment of poor-prognosis, newly diagnosed acute myeloid leukemia with ARA-C and recombinant human granulocyte-macrophage colony-stimulating factor. Blood. 1990;75:1766–1769.
   PubMed Web of Science ®Google Scholar
• Borrello IM, Levitsky HI, Stock W, et al. Granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting cellular immunotherapy in combination with autologous stem cell transplantation (ASCT) as postremission therapy for acute myeloid leukemia (AML). Blood. 2009;114:1736–1745.
   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;28:1280–1288.
   PubMed Web of Science ®Google Scholar