Developmental Therapeutics for Myelodysplastic Syndromes

Authors: Aung Naing MD 1 , Lubomir Sokol MD, PhD 1 and Alan F. List MD 1
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  • 1 From H. Lee Moffitt Cancer Center & Research Institute at the University of South Florida, College of Medicine, Tampa, Florida.

The management strategy for patients with myelodysplastic syndromes (MDS) has evolved from sole reliance on supportive measures to active treatment guided by disease risks. Recent progress in understanding the molecular pathogenesis of MDS has accelerated the discovery of new therapeutic targets, and consequently launched the development of several novel therapeutics that are currently in varied stages of clinical testing. One such agent is lenalidomide, which has shown remarkable effectiveness in the cytogenetically defined subset of MDS with the chromosome 5q31 deletion. The advent of new and effective targeted therapeutics may beneficially affect outcomes of an ever-increasing number of patients with MDS. This discussion summarizes the preliminary results of selected novel therapeutics.

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Correspondence: Alan List, MD, Chief, Division of Malignant Hematology, 12902 Magnolia Drive, SRB-4, Tampa, FL 33612-9497. E-mail: listaf@moffitt.usf.edu
  • 1.

    Vardiman JW, Hariss NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood 2002;100:2229222302.

    • Search Google Scholar
    • Export Citation
  • 2.

    Greenberg P, Cox C, Le Beau M. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 1997;89:20792088.

  • 3.

    Cheson BD, Bennett JM, Kantarjian H. Report of an international working group to standardize response criteria for myelodysplastic syndromes. Blood 2000;96:96719674.

    • Search Google Scholar
    • Export Citation
  • 4.

    Jonasova A, Neuwirtova R, Cermak J. Cyclosporin A therapy in hypoplastic MDS patients and certain refractory anemias without hypoplastic bone marrow. Br J Haematol 1998;100:304309.

    • Search Google Scholar
    • Export Citation
  • 5.

    Molldrem JJ, Leifer E, Baheci E. Antithymocyte globulin for treatment of bone marrow failure associated with myelodysplastic syndrome. Ann Intern Med 2002;137:156163.

    • Search Google Scholar
    • Export Citation
  • 6.

    Molldrem JJ, Caples M, Mavroudis D. Antithymocyte globulin for patients with myelodysplastic syndrome. Br J Haematol 1997;99:699705.

  • 7.

    Barrett AJ, Molldrem JJ, Saunthrajarian Y. Prolonged transfusion independence and disease stability in patients with myelodysplastic syndrome responding to antithymocyte globulin [abstract]. Blood 1998;92:713.

    • Search Google Scholar
    • Export Citation
  • 8.

    Saunthararajah Y, Nakamura R, Wesley R. A simple method to predict response to immunosuppressive therapy in patients with myelodysplastic syndrome. Blood 2003;102:30253027.

    • Search Google Scholar
    • Export Citation
  • 9.

    Gersuk GM, Lee JW, Beckham CA. Fas (CD95) receptor and fas ligand expression in bone marrow cells from patients with myelodysplastic syndrome. Blood 1998;88:11221123.

    • Search Google Scholar
    • Export Citation
  • 10.

    Stasi R, Amadori S. Infliximab chimaeric anti-tumour necrosis factor alpha monoclonal antibody treatment for patients with myelodysplastic syndromes [abstract]. Br J Haematol 2002;116:334.

    • Search Google Scholar
    • Export Citation
  • 11.

    Raza A, Qavi H, Lisak L. Patients with myelodysplastic syndrome benefit from palliative therapy with amifostine, pentoxyfylline, and ciprofloxacin with or without dexamethasone. Blood 2000;95:580587.

    • Search Google Scholar
    • Export Citation
  • 12.

    Grossi A, Musto P, Santini V. Combined therapy with amifostine plus erythropoietin for the treatment of myelodysplastic syndrome. Haematologica 2002;87:322323.

    • Search Google Scholar
    • Export Citation
  • 13.

    Bellamy WT, Richter L, Sirjani D. Vascular endothelial cell growth factor is an autocrine promoter of abnormal localized immature myeloid precursors and leukemia progenitor formation in myelodysplastic syndromes. Blood 2001;97:14271434.

    • Search Google Scholar
    • Export Citation
  • 14.

    Raza A, Meyer P, Dutt D. Thalidomide produces transfusion independence in long-standing refractory anemias of patients with myelodysplastic syndromes. Blood 2001;98:958965.

    • Search Google Scholar
    • Export Citation
  • 15.

    Moreno-Aspitia A, Geyer S, Li C. N998B: multicenter phase II trial of thalidomide (Thal) in adult patients with myelodysplastic syndromes (MDS) [abstract]. Blood 2002;100:96.

    • Search Google Scholar
    • Export Citation
  • 16.

    List A, Kurtin S, Roe DJ. Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med 2005;352:549557.

  • 17.

    List A, Dewald G, Bennett J. Hematologic and cytogenetic (CTG) response to lenalidomide (CC-5013) in patients with transfusion-dependent (TD) myelodysplastic syndrome (MDS) and chromosome 5q31.1 deletion: results of the multicenter MDS-003 study. J Clin Oncol 2005;23:2S.

    • Search Google Scholar
    • Export Citation
  • 18.

    List AF, Schiller GJ, Mason J. Trisenox® (arsenic trioxide) in patients with myelodysplastic syndromes (MDS): preliminary findings in a phase II clinical study [abstract]. Blood 2003;102:423.

    • Search Google Scholar
    • Export Citation
  • 19.

    Raza A, Lisak LA, Tahir S. Trilineage responses to arsenic trioxide (Trisenox®) and thalidomide in patients with myelodysplastic syndromes (MDS), particularly those with inv(3)(q21q26.2) [abstract]. Blood 2002;100:795.

    • Search Google Scholar
    • Export Citation
  • 20.

    Vey N, Dreyfus F, Guerci A. Trisenox (arsenic trioxide) in patients (pts) with myelodysplastic syndromes (MDS): preliminary results of a phase 1/2 study [abstract]. Presented at the 8th Congress of the European Hematology Association; June 12-15, 2003; Lyon, France.

    • Search Google Scholar
    • Export Citation
  • 21.

    Gotlib J, Jamieson C, List A. Phase II study of Bevacizumab (anti-VEGF humanized monoclonal antibody) in patients with myelodysplastic syndrome (MDS) [abstract]. Blood 2003;102:425.

    • Search Google Scholar
    • Export Citation
  • 22.

    Foran J, Paquette R, Copper M. A phase I study of repeated oral dosing with SU11248 for the treatment of patients with acute myeloid leukemia who have failed or are not eligible for conventional chemotherapy [abstract]. Blood 2002;100:558.

    • Search Google Scholar
    • Export Citation
  • 23.

    Giles F, Steinfeldt H, Bellamy WT. Phase 2 study of the anti-angiogenesis agent AG-013736 in patients with poor prognosis acute myeloid leukemia or myelodysplastic syndrome [abstract]. Blood 2004;104:502.

    • Search Google Scholar
    • Export Citation
  • 24.

    Reuter CWM, Morgan MA, Bergmann L. Targeting the ras signaling pathway: a rational, mechanism-based treatment for hematologic malignancies? Blood 2000;96:16551669.

    • Search Google Scholar
    • Export Citation
  • 25.

    Golub T, Barker G, Lovett M, Gilliland D. Fusion of PDGF receptor β to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation. Cell 1994;77:307316.

    • Search Google Scholar
    • Export Citation
  • 26.

    Apperley JF, Gardembas M, Melo JV. Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta. N Engl J Med 2002;347:481487.

    • Search Google Scholar
    • Export Citation
  • 27.

    Nikas SN, Drosos AA. SFCIO-469 Scios Inc. Curr Opin Investig Drugs 2004;5:12051212.

  • 28.

    Reuter CWM, Morgan MA, Bergmann L. Targeting the ras signaling pathway: a rational, mechanism-based treatment for hematologic malignancies? Blood 2000;96:16551669.

    • Search Google Scholar
    • Export Citation
  • 29.

    Kurzrock R, Kantarjian HM, Cortes J. Farnesyltransferase inhibitor R115777 in myelodysplastic syndrome: clinical and biologic activities in the phase 1 setting. Blood 2003;102:45274534.

    • Search Google Scholar
    • Export Citation
  • 30.

    Kurzrock R, Albitar M, Cortes JE. Phase II study of R115777, a farnesyl transferase inhibitor, in myelodysplastic syndrome. J Clin Oncol 2004;22:12871292.

    • Search Google Scholar
    • Export Citation
  • 31.

    Feldman EJ, Cortes J, Holyoake T. Continuous oral lonafarnib (Sarasar) for the treatment of patients with myelodysplastic syndrome [abstract]. Blood 2003;102:421.

    • Search Google Scholar
    • Export Citation
  • 32.

    Buresh A, Perentesis J, Rimsza L. Hyperleukocytosis complicating lonafarnib treatment in patients with chronic myelomonocytic leukemia. Leukemia 2005;19:308310.

    • Search Google Scholar
    • Export Citation
  • 33.

    Callander N, Ochoa-Bayona JL, Piro L. Hematologic improvement following treatment with TLK199 (Telintra™), a novel glutathione analog inhibitor of GST P1-1, in myelodysplastic syndrome (MDS): interim results of a dose-ranging phase 2a study [abstract]. Blood 2004;104:1428.

    • Search Google Scholar
    • Export Citation
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