A phase 2 study of mocetinostat, a histone deacetylase inhibitor, in relapsed or refractory lymphoma

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 treatmentrelated 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.