title: The investigational proteasome inhibitor ixazomib for the treatment of multiple myeloma.
abstract: Ixazomib is an investigational, reversible 20S proteasome inhibitor. It is the first oral proteasome inhibitor under clinical investigation in multiple myeloma (MM). Under physiological conditions, the stable citrate ester drug substance, ixazomib citrate (MLN9708), rapidly hydrolyzes to the biologically active boronic acid, ixazomib (MLN2238). Preclinical studies have demonstrated antitumor activity in MM cell lines and xenograft models. In Phase I/II clinical studies ixazomib has had generally manageable toxicities, with limited peripheral neuropathy observed to date. Preliminary data from these studies indicate ixazomib is active as a single agent in relapsed/refractory MM and as part of combination regimens in newly diagnosed patients. Phase III studies in combination with lenalidomide-dexamethasone are ongoing.
authors.affiliation: Division of Hematologic Malignancy, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Richardson
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.forename: Jacob P
authors.initials: JP
authors.lastname: Laubach
authors.forename: Neeraj
authors.initials: N
authors.lastname: Gupta
authors.forename: Ai-Min
authors.initials: AM
authors.lastname: Hui
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
authors.forename: Jesús F
authors.initials: JF
authors.lastname: San Miguel
authors.forename: Shaji
authors.initials: S
authors.lastname: Kumar
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D015507:Drugs, Investigational / Q000009:adverse effects / Q000627:therapeutic use*; D005998:Glycine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy*; D061988:Proteasome Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D001896:Boron Compounds; D015507:Drugs, Investigational; D061988:Proteasome Inhibitors; C548400:ixazomib; D005998:Glycine
keywords: continuous therapy; induction; multiple myeloma; newly diagnosed; oral administration; proteasome inhibition; refractory; relapsed