Oral HDAC inhibitor tucidinostat in patients with relapsed or refractory peripheral T-cell lymphoma: phase IIb results

Abstract

Tucidinostat (formerly known as chidamide) is an orally available, novel benzamide class of histone deacetylase (HDAC) inhibitor that selectively blocks class I and class IIb HDACs. This multicenter phase IIb study aimed to investigate the efficacy and safety of tucidinostat, 40 mg twice per week (BIW), in patients with relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL). The primary endpoint was overall response rate (ORR) assessed by an independent overall efficacy review committee. Between March 2017 and March 2019, 55 patients were treated, and 46 and 55 were evaluated for efficacy and safety, respectively. Twenty-one of 46 patients achieved objective responses with an ORR of 46% (95% confidence interval [CI]: 30.9, 61.0), including five patients with complete response (CR). Responses were observed across various PTCL subtypes. In angioimmunoblastic T-cell lymphoma, there were 2 CRs and 5 partial responses (PR) among eight patients, achieving an ORR of 88%. The disease control rate (CR + PR + stable disease) was 72% (33/46). The median progression-free survival, duration of response, and overall survival were 5.6 months, 11.5 months, 22.8 months, respectively. The most common adverse events (AEs) (all grades) were thrombocytopenia, neutropenia, leukopenia, anemia, and diarrhea. The grade ≥ 3 AEs emerging in ≥20% of patients included thrombocytopenia (51%), neutropenia (36%), lymphopenia (22%), and leukopenia (20%). Importantly, most of the AEs were manageable by supportive care and dose modification. In conclusion, the favorable efficacy and safety profiles indicate that tucidinostat would be a new therapeutic option in patients with R/R PTCL. (ClinicalTrials.gov identifier: NCT02953652)

Inhibition of HDAC2 sensitises antitumour therapy by promoting NLRP3/GSDMD‐mediated pyroptosis in colorectal cancer

“… 45 , 46 Specifically, these inhibitors have received approval for treating various hematopoietic cancers, such as cutaneous T‐cell lymphomas. 47 Our findings support the utility of HDAC2 inhibitors in colorectal treatment. SCA, a powerful and specific HDAC2 inhibitor, has been demonstrated to effectively suppresses tumour progression both in vitro and in vivo.…”

Improving gastrointestinal quality of life: romidepsin to tucidinostat in a case of angioimmunoblastic T cell lymphoma

“…Recent research from China has confirmed the efficacy and safety of tucidinostat as a maintenance treatment for patients with PTCL 13. Meanwhile, Japanese phase II studies of tucidinostat10 and romidepsin14 indicate comparable overall response rate and progression-free survival, but their safety profiles appear to be somewhat different. Both drugs commonly induce haematological toxicity, while tucidinostat has a lower incidence of non-haematological side effects such as nausea, vomiting, constipation, anorexia and fatigue when compared with romidepsin.…”

“…Recently, tucidinostat (formerly known as chidamide), a novel oral HDAC inhibitor that selectively targets class I and class IIb HDACs, received approval from the Chinese Food and Drug Administration in 20149 and from the Japanese Ministry of Health, Labour, and Welfare in 202110 for the treatment of R/R PTCL. Furthermore, several clinical trials with tucidinostat are currently ongoing in the USA, as monotherapy or in combination with other therapies, for both haematological and solid tumours.…”

Aggressive T‐cell lymphomas: 2024: Updates on diagnosis, risk stratification, and management

“…• Tucidinostat in R/R PTCL (n = 46), ORR 46%, ORR 88% in AITL, median DOR 11.5 months 112 Hypomethylating agent…”