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

被引：43

作者：

Sborov, Douglas W. ^{[1
]}

Canella, Alessandro ^{[2
]}

Hade, Erinn M. ^{[3
]}

Mo, Xiaokui ^{[3
]}

Khountham, Soun ^{[2
]}

Wang, Jiang ^{[2
]}

Ni, Wenjun ^{[4
]}

Poi, Ming ^{[2
,4
]}

Coss, Christopher ^{[2
,4
]}

Liu, Zhongfa ^{[4
]}

Phelps, Mitch A. ^{[2
,4
]}

Mortazavi, Amir ^{[5
]}

Andritsos, Leslie ^{[6
]}

Baiocchi, Robert A. ^{[6
]}

Christian, Beth A. ^{[6
]}

Benson, Don M. ^{[6
]}

Flynn, Joseph ^{[6
]}

Porcu, Pierluigi ^{[6
]}

Byrd, John C. ^{[6
]}

Pichiorri, Flavia ^{[7
]}

Hofmeister, Craig C. ^{[6
]}

机构：

[1] Univ Utah, Dept Internal Med, Div Hematol, Salt Lake City, UT 84112 USA

[2] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA

[3] Ohio State Univ, Dept Biomed Informat, Ctr Biostat, Columbus, OH 43210 USA

[4] Ohio State Univ, Coll Pharm, Div Pharmaceut, 500 W 12th Ave, Columbus, OH 43210 USA

[5] Ohio State Univ, Dept Internal Med, Div Med Oncol, Columbus, OH 43210 USA

[6] Ohio State Univ, Dept Internal Med, Div Hematol, Columbus, OH 43210 USA

[7] City Hope Natl Med Ctr, Ctr Comprehens Canc, Duarte, CA USA

来源：

LEUKEMIA & LYMPHOMA | 2017年 / 58卷 / 10期

关键词：

Histone deacetylase inhibitor; multiple myeloma; lymphoma; phase; 1; pharmacokinetics; HISTONE-DEACETYLASE INHIBITOR; SUBEROYLANILIDE HYDROXAMIC ACID; RESPONSE CRITERIA; II TRIAL; PANOBINOSTAT; VORINOSTAT; BORTEZOMIB; DEXAMETHASONE; MULTICENTER; COMBINATION;

D O I：

10.1080/10428194.2017.1298751

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 40mg 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.

引用

页码：2310 / 2318

页数：9

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