A phase 1 trial of the HDAC inhibitor AR-42 in patients with multiple myeloma and T- and B-cell lymphomas.

Abstract

Histone deacetylase inhibitors (HDACi) have proven activity in hematologic malignancies, and their FDA approval in multiple myeloma (MM) and T-cell lymphoma highlights the need for further development of this drug class. We investigated AR-42, an oral pan-HDACi, in a first-in-man phase 1 dose escalation clinical trial. Overall, treatment was well tolerated, no DLTs were evident, and the MTD was defined as 40 mg dosed three times weekly for three weeks of a 28-day cycle. One patient each with MM and mantle cell lymphoma demonstrated disease control for 19 and 27 months (ongoing), respectively. Treatment was associated with reduction of serum CD44, a transmembrane glycoprotein associated with steroid and immunomodulatory drug resistance in MM. Our findings indicate that AR-42 is safe and that further investigation of AR-42 in combination regimens for the treatment of patients with lymphoma and MM is warranted.

TRIAL REGISTRATION:

http://clinicaltrials.gov/ct2/show/NCT01129193.

• Authors: Douglas W Sborov, Alessandro Canella, Erinn M Hade, Xiaokui Mo, Soun Khountham, Jiang Wang, Wenjun Ni, Ming Poi, Christopher Coss, Zhongfa Liu, Mitch A Phelps, Amir Mortazavi, Leslie Andritsos, Robert A Baiocchi, Beth A Christian, Don M Benson, Joseph Flynn, Pierluigi Porcu, John C Byrd, Flavia Pichiorri, Craig C Hofmeister
• Journal: Leukemia & lymphoma (Leuk Lymphoma) Vol. 58 Issue 10 Pg. 2310-2318 (Oct 2017) ISSN: 1029-2403 [Electronic] United States
• PMID: 28270022 (Publication Type: Clinical Trial, Phase I, Journal Article)

Chemical References

• HDAC-42
• Histone Deacetylase Inhibitors
• Phenylbutyrates

Topics

• Histone Deacetylase Inhibitors (adverse effects, therapeutic use)
• Humans
• Lymphoma, B-Cell (drug therapy)
• Multiple Myeloma (drug therapy)
• Phenylbutyrates (adverse effects, therapeutic use)