title: Ixazomib for the treatment of multiple myeloma.
abstract: BACKGROUND
  Proteasome inhibition is a mainstay in the treatment of multiple myeloma (MM). Bortezomib, the first proteasome inhibitor (PI) approved for MM therapy, has shown efficacy in relapsed/refractory patients and in the front-line setting. Among second-generation PIs, MLN9708 ( ixazomib ) is the first oral compound to be evaluated in MM treatment and has shown improvement in pharmacokinetic and pharmacodynamic parameters compared with bortezomib with a similar efficacy in the control of myeloma growth and in the prevention of bone loss.
  
  
  METHODS
  In this review, the authors discuss the rationale for use of PIs. They then summarize the clinical development of ixazomib in MM, from initial Phase I to Phase II studies as a monotherapy and in combination with other chemotherapeutics.
  
  
  CONCLUSIONS
  Preliminary data of Phase I/II trials showed that ixazomib had a good safety profile and exerted anti-myeloma activity as a single agent in relapsed/refractory patients. Furthermore, ixazomib also had efficacy in patients who were refractory to bortezomib. Its use in combination with lenalidomide and dexamethasone was shown to be an effective and well-tolerated regimen in up-front treatment leading to minimal residual disease negativity in a significant number of patients. Results of Phase III trials, evaluating ixazomib in induction or maintenance therapy, are awaited.
authors.affiliation: Dipartimento Oncoematologico, Unità Operativa Complessa di Ematologia, Azienda Ospedaliera di Cosenza , Viale della Repubblica, 87100 Cosenza , Italy +39 0984 681329 ; +39 0984 681866 ; massim.gentile@tiscali.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Gentile
authors.forename: Massimo
authors.initials: M
authors.lastname: Offidani
authors.forename: Ernesto
authors.initials: E
authors.lastname: Vigna
authors.forename: Laura
authors.initials: L
authors.lastname: Corvatta
authors.forename: Anna Grazia
authors.initials: AG
authors.lastname: Recchia
authors.forename: Lucio
authors.initials: L
authors.lastname: Morabito
authors.forename: Fortunato
authors.initials: F
authors.lastname: Morabito
authors.forename: Silvia
authors.initials: S
authors.lastname: Gentili
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D001896:Boron Compounds / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D005998:Glycine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D061988:Proteasome Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D001896:Boron Compounds; D061988:Proteasome Inhibitors; C548400:ixazomib; D005998:Glycine
keywords: MNL9708; ixazomib; multiple myeloma; proteasome inhibitors