Missing content? – Request curation!
Request curation for specific Genes, variants, or PubMed publications.
Have questions, comments or suggestions? - Let us know!
Email us at : email@example.com
|Ref Type||Journal Article|
|Authors||Vogl DT, Raje N, Jagannath S, Richardson P, Hari P, Orlowski R, Supko JG, Tamang D, Yang M, Jones SS, Wheeler C, Markelewicz RJ, Lonial S|
|Title||Ricolinostat, the First Selective Histone Deacetylase 6 Inhibitor, in Combination with Bortezomib and Dexamethasone for Relapsed or Refractory Multiple Myeloma.|
|Journal||Clinical cancer research : an official journal of the American Association for Cancer Research|
|Date||2017 07 01|
|Abstract Text||Purpose: Histone deacetylase (HDAC) inhibition improves the efficacy of proteasome inhibition for multiple myeloma but adds substantial toxicity. Preclinical models suggest that the observed synergy is due to the role of HDAC6 in mediating resistance to proteasome inhibition via the aggresome/autophagy pathway of protein degradation.Experimental Design: We conducted a phase I/II trial of the HDAC6-selective inhibitor ricolinostat to define the safety, preliminary efficacy, and recommended phase II dose in combination with standard proteasome inhibitor therapy. Patients with relapsed or refractory multiple myeloma received oral ricolinostat on days 1-5 and 8-12 of each 21-day cycle.Results: Single-agent ricolinostat therapy resulted in neither significant toxicity nor clinical responses. Combination therapy with bortezomib and dexamethasone was well-tolerated during dose escalation but led to dose-limiting diarrhea in an expansion cohort at a ricolinostat dose of 160 mg twice daily. Combination therapy at a ricolinostat dose of 160 mg daily in a second expansion cohort was well tolerated, with less severe hematologic, gastrointestinal, and constitutional toxicities compared with published data on nonselective HDAC inhibitors. The overall response rate in combination with daily ricolinostat at ≥160 mg was 37%. The response rate to combination therapy among bortezomib-refractory patients was 14%. Samples taken during therapy showed dose-dependent increases of acetylated tubulin in peripheral blood lymphocytes.Conclusions: At the recommended phase II dose of ricolinostat of 160 mg daily, the combination with bortezomib and dexamethasone is safe, well-tolerated, and active, suggesting that selective inhibition of HDAC6 is a promising approach to multiple myeloma therapy. Clin Cancer Res; 23(13); 3307-15. ©2017 AACR.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|Unknown unknown||multiple myeloma||no benefit||Ricolinostat||Phase Ib/II||Actionable||In a Phase Ib/II trial, Ricolinostat (ACY-1215) as a single therapy did not result in toxicity nor clinical benefit in multiple myeloma patients (PMID: 28053023).||28053023|
|Unknown unknown||multiple myeloma||not applicable||Bortezomib + Dexamethasone + Ricolinostat||Phase Ib/II||Actionable||In a Phase Ib/II trial, the Phase II recommended dose of Ricolinostat (ACY-1215) combined with Velcade (bortezomib) and Adexone (dexamethasone) resulted in safety and tolerance, and an overall response rate of 37% in patients with multiple myeloma (PMID: 28053023).||28053023|