Infliximab chimeric antitumor necrosis factor-a monoclonal antibody as potential treatment for myelodysplastic syndromes

Abstract

Accumulating evidence indicates tumor necrosis factor-a (TNF-a) as a key cytokine in the pathogenesis of the myelodysplastic syndromes (MDS). The identification of TNF-a as a regulator of apoptosis and the increased susceptibility of MDS cells to this cytokine provided the basis for several clinical trials of TNF inhibitors. Infliximab is an IgG1 chimeric anti-TNF-a monoclonal antibody composed of human constant and murine variable regions that bind specifically to both soluble and membrane-bound TNF-a. To date, only 2 studies have investigated the use of infliximab in patients with low-risk MDS. In both reports the drug showed a limited but significant activity and a favorable side-effect profile. In some patients, hematopoietic response was associated with decreased apoptosis as well as a decrease in abnormal metaphases by 50%. Further studies are currently underway and should provide useful information to define the more responsive subtypes of MDS, the patient characteristics, and the proper dosing regimen.