Filanesib With Bortezomib and Dexamethasone Active in Myeloma

The combination of filanesib, bortezomib, and dexamethasone appears to have durable activity, with a favorable safety profile, for patients with recurrent/refractory multiple myeloma, according to an article published in Cancer.¹

Filanesib is a kinesin spindle protein inhibitor that has a mechanism of action distinct from available multiple myeloma therapies. The novel agent has demonstrated activity in patients with recurrent/refractory multiple myeloma, and has exhibited synergy with bortezomib in preclinical trials; for this phase 1 study, researchers evaluated the tolerability and activity of filanesib in combination with bortezomib and dexamethasone.

Patients with relapsed/refractory disease were enrolled into an initial dose-escalation phase to determine the maximum tolerated dose of 2 schedules of the treatment regimen. Patients had received a median of 3 prior lines of therapy; 56% were refractory to proteasome inhibitors.

The overall response rate was 20% (55 patients), and was 29% for 14 patients refractory to proteasome inhibitors receiving filanesib at a dose of 1.25 mg/m² or higher. Responses ranged in duration from 5.2 months to more than 21.2 months.

The most common toxicities were transient, noncumulative neutropenia and thrombocytopenia; grade 3 to 4 events were reported in 44% and 29% of patients, respectively. Only 16% of patients reported grade 3 to 4 neutropenia in cycle 1 with filgastrim, suggesting manageable hematologic toxicity.

No more than 11% of patients reported nonhematologic grade 3 to 4 adverse events.

The safety and efficacy of filanesib are being evaluated in phase 2 trials as a single agent and in combination with carfilzomib for patients with relapsed/refractory multiple myeloma.                                      

Reference

1. Chari A, Htut M, Zonder JA, et al. A phase 1 dose-escalation study of filanesib plus bortezomib and dexamethasone in patients with recurrent/refractory multiple myeloma. Cancer. 2016 Jul 9. doi: 10.1002/cncr.30174 [Epub ahead of print]