Filanesib plus bortezomib and dexamethasone in relapsed/refractory t(11;14) and 1q21 gain multiple myeloma. (17th December 2021)

• Record Type: Journal Article
• Authors: Pan, Darren; Kaufman, Jonathan L.; Htut, Myo; Agrawal, Manish; Mazumder, Amitabha; Cornell, Robert F.; Zonder, Jeffrey A.; Fay, Joseph W.; Modiano, Manuel R.; Moshier, Erin L.; Rush, Selena A.; Tunquist, Brian J.; Chari, Ajai
• Is Part Of: Cancer medicine. Volume 11:Number 2(2022)
• Page Start: 358
• Page End: 370
• Publication Date: 2021-12-17
• Subjects: chemotherapy -- clinical cancer research -- clinical trials -- experimental -- medical oncology -- multiple myeloma -- therapeutics; 616.994005
• DOI: 10.1002/cam4.4451
• Languages: English
• ISSNs: 2045-7634

Abstract

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 : We report on the final analysis of the phase 1 trial of filanesib, bortezomib, and dexamethasone in relapsed/refractory multiple myeloma. Among patients receiving therapeutic doses of the study drugs, overall response rate was 39% with median duration of response of 14.1 months and median progression‐free survival of 8.0 months. The combination continues to show safety and encouraging activity in this population, particularly in those patients with 1q21 gain and t(11;14).