Tucidinostat, a promising therapeutic option for R/R peripheral T-cell lymphoma

March 2023 Clinical trials Andrea Enguita

Patients with relapsed/refractory (R/R) peripheral T-cell lymphoma PTCL have a poor prognosis. Interestingly, class I histone deacetylase (HDAC) is overexpressed in PTCL, regardless of the subtype. According to the results of a phase IIb trial published in Haematologica, the HDAC inhibitor tucidinostat displays favourable efficacy and safety outcomes on patients with R/R PTCL, suggesting that tucidinostat could become a new therapeutic option in this setting.

Peripheral T-cell lymphoma (PTCL) is a rare and heterogeneous disease entity that encompasses different subtypes, including PTCL, not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic large-cell lymphoma (ALCL). Treatment responses are rarely durable in most PTCL subtypes, and patients with relapsed/refractory (R/R) PTCL have a dismal outcome, with a median survival after the first relapse of less than 6 months. Interestingly, several studies have shown that the class I histone deacetylases (HDAC) 1 and 2 are overexpressed in PTCL, regardless of the subtype. Tucidinostat, an orally available, novel benzamide class of HDAC inhibitor that selectively blocks class I and IIb HDAC, has already shown promising results in previous studies. This multicentre phase IIb study investigated the efficacy and safety of tucidinostat in patients with R/R PTCL.

Study findings

This multicentre, single-arm, phase IIb study was conducted in Japan and South Korea to investigate the efficacy and safety of tucidinostat, 40 mg twice per week, in patients with R/R PTCL. In total, 55 patients were treated, of whom 46 were evaluated for efficacy. The most common subtypes were PTCL-NOS (n=34), followed by AITL (n=8). The primary endpoint was overall response rate (ORR). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS) and safety.

After a median follow-up of 8.3 months, ORR was reported at 46%, including five patients with a complete relapse (11%). Remarkably, the ORR was relatively higher in patients with AITL (88%). The median PFS, DOR, and OS were reported at 5.6, 11.5 months, 22.8 months, respectively. Regarding safety, most of the adverse events (AEs) were manageable by supportive care and dose modification. The most common AE were thrombocytopenia, neutropenia, leukopenia, anaemia, and diarrhoea.

In conclusion, the favourable efficacy and safety results indicate that tucidinostat could be a promising new therapeutic option for patients with R/R PTCL. Of note, tucidinostat is orally available and, thus, it may be more convenient in the outpatient setting than conventional cytotoxic agents or other novel intravenous agents for R/R PTCL.


Rai S, Kim WS, Ando K, et al. Oral HDAC inhibitor tucidinostat in patients with relapsed or refractory peripheral T-cell lymphoma: phase IIb results. Haematologica. 2023;108(3):811-21.