Current treatment options in patients with mastocytosis: status in 2015 and future perspectives

Mastocytosis is a term referring to a heterogeneous group of disorders characterized by abnormal mast cell (MC) accumulation in the skin and/or internal organs. In children, the disease involves mostly the skin (cutaneous mastocytosis; CM), whereas in adults, the disease is usually systemic (systemic mastocytosis; SM). Advanced SM variants with end-organ damage and reduced life expectancy have also been described, but are rare. Clinical signs and symptoms in SM result from excessive mediator release by MCs and, in aggressive forms, from organ failure related to MC infiltration. As a consequence, treatment of indolent SM aims primarily at the control of symptoms caused by MC mediator release. By contrast, in advanced SM, such as aggressive SM, MC leukemia, and MC sarcoma, intensive (chemo)therapy with or without allogeneic stem cell transplantation has to be considered. In addition, activating mutations in KIT (mostly KIT D816V in adults) are found in most patients with SM, so that targeted therapies aimed at blocking mutant KIT variants or/and downstream signaling pathways are currently being developed. Other targets, such as specific surface antigens expressed on neoplastic MCs, might be considered for the development of future therapies in advanced SM.