Monoclonal Antibodies for the Treatment of Multiple Myeloma—A New Paradigm

Abstract

The past decade has seen many promising new therapies emerge for the treatment of multiple myeloma (MM), resulting in improved survival of patients. Despite these improvements, the disease eventually becomes refractory to the available options and patients die of progressive disease. Development of new therapies with new modes of action remains critical for the continued improvement in outcome, and given the success of monoclonal antibodies (MoAbs) in other cancers there has been considerable interest in development of this class of drugs for MM. Past attempts with MoAbs against interleukin-6 (IL-6) as well as vascular endothelial growth factor (VEGF) targeted antibodies have not realized the potential. More recently, development of MoAbs against SLAMF7 and cluster of differentiation 38 (CD38) have demonstrated considerable activity in MM, the former in combination and the latter as a single agents. At present, it remains to be defined how MoAb therapy can be most effectively incorporated into the current therapeutic paradigms that will help to achieve longer disease control and significant survival gains in patients with MM, either as short-term induction therapy, frontline treatment in transplant ineligible patients, or long-term maintenance therapy post autologous hematopoietic stem cell transplantation (ASCT)/induction cytotoxic therapy. Ongoing studies are examining the potential of several other targets on the plasma cell, using both naked antibodies as well as toxin conjugated MoAbs.