TNF-α targeted therapeutic approaches in patients with hematologic malignancies

Tumor necrosis factor (TNF)-α 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-α are being evaluated in clinical trials. This review describes the development of the soluble TNF-α receptor (p75 TNF-R: Fc; etanercept) and other agents inactivating or blocking TNF-α 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.