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A phase 2 study of mocetinostat, a histone deacetylase inhibitor, in relapsed or refractory lymphoma
Author(s) -
Batlevi Connie L.,
Crump Michael,
Andreadis Charalambos,
Rizzieri David,
Assouline Sarit E.,
Fox Susan,
Jagt Richard H. C.,
Copeland Amanda,
Potvin Diane,
Chao Richard,
Younes Anas
Publication year - 2017
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.14698
Subject(s) - medicine , histone deacetylase inhibitor , follicular lymphoma , oncology , adverse effect , diffuse large b cell lymphoma , refractory (planetary science) , lymphoma , aggressive lymphoma , gastroenterology , histone deacetylase , rituximab , biology , histone , biochemistry , astrobiology , gene
Summary Deregulation of histone deacetylase ( HDAC ) is important in the pathogenesis of follicular lymphoma ( FL ) and diffuse large B‐cell lymphoma ( DLBCL ). Mocetinostat, an isotype‐selective HDAC inhibitor, induces accumulation of acetylated histones, cell cycle arrest and apoptosis in several cancers. This phase 2 study evaluated mocetinostat in patients with relapsed/refractory (R/R) DLBCL and FL . Seventy‐two patients received mocetinostat (starting doses: 70–110 mg TIW , 4‐week cycles). The best overall response rate (95% CI ) was 18·9% (7·2, 32·2) for the DLBCL cohort ( n = 41), and 11·5% (1·7, 20·7) for the FL cohort ( n = 31). Responses were durable (≥90 days in 7 of 10 responses). Overall, 54·1% and 73·1% of patients derived clinical benefit (response or stable disease) from mocetinostat in the DLBCL and FL cohorts, respectively. Progression‐free survival ranged from 1·8 to 22·8 months and 11·8 to 26·3 months in responders with DLBCL and FL , respectively. The most frequent treatment‐related adverse events were fatigue (75·0%), nausea (69·4%) and diarrhoea (61·1%). Although mocetinostat had limited single‐agent activity in R/R DLBCL and FL , patients with clinical benefit had long‐term disease control. The safety profile was acceptable. This drug class warrants further investigation, including identifying patients more likely to respond to this agent, or in combination with other agents.