Filanesib With Bortezomib and Dexamethasone Active in Myeloma

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The combination of filanesib, bortezomib, and dexamethasone appears to have durable activity in multiple myeloma.
The combination of filanesib, bortezomib, and dexamethasone appears to have durable activity in multiple 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.

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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]

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