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

Autor: Pan D; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Kaufman JL; Winship Cancer Institute, Emory University, Atlanta, Georgia, USA., Htut M; City of Hope National Medical Center, Duarte, California, USA., Agrawal M; Maryland Oncology Hematology, Columbia, Maryland, USA., Mazumder A; The Oncology Institute of Hope and Innovation, Glendale, California, USA., Cornell RF; Vanderbilt University Medical Center, Nashville, Tennessee, USA., Zonder JA; Karmanos Cancer Institute, Detroit, Michigan, USA., Fay JW; Texas Oncology Baylor Charles A Sammons Cancer Center, Dallas, Texas, USA., Modiano MR; Arizona Clinical Research Center, Hematology Oncology, Tucson, Arizona, USA., Moshier EL; Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Rush SA; Pfizer, New York, New York, USA., Tunquist BJ; Pfizer, New York, New York, USA., Chari A; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Jazyk: angličtina
Zdroj: Cancer medicine [Cancer Med] 2022 Jan; Vol. 11 (2), pp. 358-370. Date of Electronic Publication: 2021 Dec 17.
DOI: 10.1002/cam4.4451
Abstrakt: 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).
(© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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