Ixazomib for the treatment of multiple myeloma.

Abstract

INTRODUCTION:

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.

AREAS COVERED:

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.

EXPERT OPINION:

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: Massimo Gentile, Massimo Offidani, Ernesto Vigna, Laura Corvatta, Anna Grazia Recchia, Lucio Morabito, Fortunato Morabito, Silvia Gentili
• Journal: Expert opinion on investigational drugs (Expert Opin Investig Drugs) Vol. 24 Issue 9 Pg. 1287-98 ( 2015) ISSN: 1744-7658 [Electronic] England
• PMID: 26138345 (Publication Type: Journal Article, Review)

Chemical References

• Antineoplastic Agents
• Boron Compounds
• Proteasome Inhibitors
• ixazomib
• Glycine

Topics

• Antineoplastic Agents (adverse effects, pharmacology, therapeutic use)
• Boron Compounds (adverse effects, pharmacology, therapeutic use)
• Clinical Trials, Phase I as Topic
• Clinical Trials, Phase II as Topic
• Glycine (adverse effects, analogs & derivatives, pharmacology, therapeutic use)
• Humans
• Multiple Myeloma (drug therapy, pathology)
• Proteasome Inhibitors (adverse effects, pharmacology, therapeutic use)