Cytotoxic efficacy of filanesib and melphalan combination is governed by sequence of treatment in human myeloma cells

The integration of novel agents (for example, proteasome inhibitors, IMiDS) into frontline therapy for multiple myeloma (MM) has significantly improved response rates and increased progression-free survival. Nevertheless, most patients with MM relapse often with resistant disease. Several clinical trials assessing the current role of high-dose chemotherapy (HDT) with autologous stem cell transplant (ASCT) have reaffirmed the utility of HDT-ASCT for treating transplant-eligible MM patients. Efforts to improve the standard conditioning regimen (single agent melphalan 200 mg/m) for ASCT have generally failed due to increased toxicity without the demonstration of superiority. However, recent evidence suggests that conditioning regimens combining HDT-melphalan with novel agents (bortezomib, lenalidomide) are safer and improve patient response and outcome. Filanesib (ARRY-520) is a first-in-class, small-molecule inhibitor of Kinesin Spindle Protein (KSP) with activity in MM refractory to standard of care agents. Filanesib inhibits mitotic spindle pole