학술논문

Filanesib plus bortezomib and dexamethasone in relapsed/refractory t(11;14) and 1q21 gain multiple myeloma.
Document Type
Article
Source
Cancer Medicine. Jan2022, Vol. 11 Issue 2, p358-370. 13p.
Subject
*MULTIPLE myeloma
*BORTEZOMIB
*DEXAMETHASONE
*PROGRESSION-free survival
*SURVIVAL rate
Language
ISSN
2045-7634
Abstract
Filanesib is a first‐in‐class kinesin spindle protein inhibitor which demonstrated safety and encouraging activity in combination with bortezomib and dexamethasone in relapsed/refractory multiple myeloma in a preliminary analysis of dose‐escalation phase results. This multicenter study included first a dose‐escalation phase to determine maximum tolerated dose of two schedules of filanesib, bortezomib, and dexamethasone and a subsequent dose‐expansion phase using the maximum tolerated doses. In the dose‐expansion phase, 28 patients were evaluable for safety and efficacy. The most common grade ≥3 adverse events were neutropenia (21%) and anemia (18%), which were noncumulative and reversible, and hypertension (18%). The overall response rate was 43% with median duration of response not yet reached (range, 2.8–23.7+ months) with median follow‐up of 6.3 months. A post hoc analysis incorporated 29 dose‐escalation phase patients who received therapeutic filanesib doses, with an overall response rate of 39% and median duration of response of 18.0 months among the 57 total patients with median progression‐free survival of 8.5 months. Notably, the PFS of high risk patients was comparable at 8.5 months, driven by the patients with 1q21 gain, characterized by increased MCL‐1 expression, with a PFS of 9.1 months versus 3.5 months for the remainder of high risk patients. Patients with t(11;14) also had an encouraging PFS of 15.0 months. The combination of filanesib, bortezomib, and dexamethasone continues to show safety and encouraging activity in relapsed/refractory multiple myeloma, particularly in those patients with 1q21 gain and t(11;14). [ABSTRACT FROM AUTHOR]