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Deacetylase inhibitors: an advance in myeloma therapy?
- Source :
-
Expert review of hematology [Expert Rev Hematol] 2017 Mar; Vol. 10 (3), pp. 229-237. Date of Electronic Publication: 2017 Feb 01. - Publication Year :
- 2017
-
Abstract
- Introduction: A significant unmet need exists in patients with relapsed or refractory multiple myeloma (MM), which remains an incurable disease despite recent advances in the field. One such development was the use of deacetylase inhibitors (DACi), which exert unique antimyeloma effects through targeting of epigenetic and protein metabolism pathways. The pan-DACi panobinostat was recently approved in combination with bortezomib and dexamethasone for use in patients with relapsed or relapsed and refractory MM. Results of a phase 3 trial showed that the panobinostat-containing regimen improved the overall response rate and progression-free survival. Panobinostat-associated adverse events included thrombocytopenia, diarrhea, fatigue, and peripheral neuropathy. Research into how to maintain the benefits of DACi while improving tolerability is ongoing. Areas covered: This review focuses on the efficacy and safety of panobinostat and panobinostat-based combinations for MM. Early data from clinical trials investigating the HDAC6 inhibitor ricolinostat are also discussed. Expert commentary: DACi are a unique and effective new class of agents for the treatment of MM, with panobinostat being the first to have clinically meaningful benefit for patients with relapsed or refractory MM. Optimization of dose and schedule, novel combination strategies, and introduction of selective DACi may improve the risk-benefit profile of DACi-based regimens.
- Subjects :
- Antineoplastic Agents pharmacology
Antineoplastic Combined Chemotherapy Protocols adverse effects
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Bortezomib administration & dosage
Clinical Trials as Topic
Dexamethasone administration & dosage
Drug Discovery
Drug Resistance, Neoplasm
Epigenesis, Genetic drug effects
Histone Deacetylase Inhibitors pharmacology
Humans
Hydroxamic Acids pharmacology
Hydroxamic Acids therapeutic use
Indoles pharmacology
Indoles therapeutic use
Multiple Myeloma diagnosis
Multiple Myeloma genetics
Multiple Myeloma metabolism
Panobinostat
Recurrence
Antineoplastic Agents therapeutic use
Histone Deacetylase Inhibitors therapeutic use
Molecular Targeted Therapy
Multiple Myeloma drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1747-4094
- Volume :
- 10
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Expert review of hematology
- Publication Type :
- Academic Journal
- Accession number :
- 28076695
- Full Text :
- https://doi.org/10.1080/17474086.2017.1280388