TNF-alpha targeted therapeutic approaches in patients with hematologic malignancies.
Tumor necrosis factor (TNF)-alpha is a major effector and regulatory cytokine with a pleiotropic role in the pathogenesis of several immune-regulated diseases, including graft versus host disease (GVHD) and hematologic malignancies, such as multiple myeloma (MM), myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). Curative treatment for the above diseases are not currently available for most patients. Therapeutic approaches inactivating or blocking TNF-alpha are being evaluated in clinical trials. This review describes the development of the soluble TNF-alpha receptor (p75 TNF-R: Fc; etanercept) and other agents inactivating or blocking TNF-alpha in the management of patients with hematologic malignancies. The satisfactory safety profile of etanercept--as demonstrated in patients with autoimmune diseases--has been confirmed in patients with hematologic malignancies and GVHD. Studies to assess whether etanercept, either as a single agent or in combination with cytotoxic and/or immune therapy, may increase response rates and/or survival in patients with MM, MDS, AML and other hematologic malignancies are now warranted.
Department of Lukemia, Box 428, University of Texas M.D. Anderson Cancer Center, 1400 Holcombe Boulevard, Houston, TX 77030, USA.
Apostolia-Maria
AM
Tsimberidou
Francis J
FJ
Giles
D000970:Antineoplastic Agents / Q000627:therapeutic use; D000068800:Etanercept; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000276:immunology; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000276:immunology; D009101:Multiple Myeloma / Q000188:drug therapy / Q000276:immunology; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000276:immunology; D055728:Primary Myelofibrosis / Q000188:drug therapy / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
D000970:Antineoplastic Agents; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept