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On 25th April 2017, Connie L. Batlevi from the Memorial Sloan-Kettering Cancer Center, New York, NY, USA, and colleagues published in the British Journal of Haematology the results of their phase II, open-label, non-randomized, multicenter trial of mocetinostat in patients with R/R DLBCL and FL (NCT00359086).
In total, 72 patients were treated with the HDAC inhibitor mocetinostat; the median age of the 41 DLBCL patients was 60 years (range, 31–80 years) and for the 31 FL patients was 64 years (range, 36–76 years).
Oral mocetinostat was administered 3 times a week in 4-week cycles (i.e. 12 doses per 28-day cycle) until disease progression, unacceptable toxicity, or discontinuation for any other reason. The initial starting dose was 110mg; however, in subsequent protocol amendments, starting dose was reduced to 85mg and then to 70mg. The median number of cycles per patient was 3 (range, 1–23).
The group concluded that their study shows that oral mocetinostat administered 3 times a week and dosed at 70–110mg “has limited single-agent activity in patients with R/R DLBCL and FL” and has an “acceptable and manageable” toxicity profile. Furthermore, the group suggest that mocetinostat should be investigated in combination with other agents in the future.
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.
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