학술논문
A phase 1 trial of the HDAC inhibitor AR-42 in patients with multiple myeloma and T- and B-cell lymphomas.
Document Type
Article
Author
Sborov, Douglas W.; Canella, Alessandro; Hade, Erinn M.; Mo, Xiaokui; Khountham, Soun; Wang, Jiang; Ni, Wenjun; Poi, Ming; Coss, Christopher; Liu, Zhongfa; Phelps, Mitch A.; Mortazavi, Amir; Andritsos, Leslie; Baiocchi, Robert A.; Christian, Beth A.; Benson, Don M.; Flynn, Joseph; Porcu, Pierluigi; Byrd, John C.; Pichiorri, Flavia
Source
Subject
*HISTONE deacetylase inhibitors
*MULTIPLE myeloma
*T cells
*B cell lymphoma
*MANTLE cell lymphoma
*PATIENTS
*TUMORS
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Language
ISSN
1042-8194
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 [ABSTRACT FROM PUBLISHER]