Proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs) are integral components of treatment regimens for multiple myeloma (MM). However, prognosis of patients refractory to these agents is poor, with limited treatment options, underscoring the need for agents with novel mechanisms of action. Filanesib (ARRY-520) is a first-in-class kinesin spindle protein inhibitor that has demonstrated promising clinical activity in combination with PIs, including bortezomib and carfilzomib in patients with MM refractory to PIs and IMiDs.1,2 An ongoing, randomized, open-label phase 2 study is evaluating the combination of carfilzomib plus filanesib versus carfilzomib alone in patients with relapsed and/or refractory MM. Zonder and colleagues reported preliminary results of this trial at the ASH 2015 meeting.3 At the time of this analysis, 72 patients who had received at least 2 prior regimens, including bortezomib and an IMiD, and were refractory to the last regimen, have been randomized 2:1 to receive either carfilzomib (20/27 mg/m2 intravenously) plus filasenib (1.25 mg/m2 intravenously) (n = 49) or carfilzomib alone (n = 23); of these, 50 patients were evaluable for this analysis. In this heavily pretreated patient population (median prior regimens 4-5 for the 2 arms), carfilzomib/filanesib treatment resulted in an objective response rate (ORR) of 30%, including 3 very good partial responses and 6 partial responses compared with 10% with carfilzomib alone. Notably, the patient subset with double-refractory disease to IMiDs and bortezomib achieved an ORR of 35% with combination therapy compared with 14% with control. Grade 3/4 hematologic laboratory abnormalities were higher with carfilzomib/filanesib therapy and included leukopenia (21% vs 9%), neutropenia (24% vs 14%), thrombocytopenia (24% vs 14%), and anemia (26% vs 9%). Dyspnea was the only grade 3/4 nonhematologic adverse event reported (5% vs 11%). Based on these preliminary study results, carfilzomib plus filanesib appears to be a promising steroid-sparing alternate treatment option for patients with relapsed and/or refractory MM, including those with double-refractory disease.
