Results from a multicenter, open-label, pivotal phase II study of chidamide in relapsed or refractory peripheral T-cell lymphoma.

Chidamide is a novel benzamide type of subtype-selective histone deacetylase (HDAC) inhibitor with unique mechanisms of action compared with marketed HDAC inhibitors. This phase II study was to evaluate the efficacy and safety of chidamide in relapsed or refractory peripheral T-cell lymphoma (PTCL) in Chinese population. Patients with relapsed or refractory PTCL of different subtypes received chidamide of 30 mg orally twice per week. The primary end point was overall response rate (ORR). Responding patients should be confirmed at least 4 weeks after the criteria of the response were first met, and were reviewed by an independent review committee. Eighty-three patients were enrolled and 79 patients with eligible PTCL histology were for efficacy assessments. Patients enrolled over 10% were with subtypes of PTCL not otherwise specified (34%), anaplastic large-cell lymphoma (22%), extranodal natural killer (NK)/T-cell lymphoma, nasal type (20%), or angioimmunoblastic T-cell lymphoma (AITL, 13%). The ORR was 28% (22 of 79) including 14% (11 of 79) with complete response/unconfirmed complete response (CR/CRu). Median progression-free survival and overall survival were 2.1 and 21.4 months, respectively. AITL patients tended to have higher ORR (50%) and CR/CRu rate (40%), as well as more durable responses, to chidamide treatment. Most adverse events (AEs) were grade 1 or 2, and AEs ≥grade 3 that occurred in ≥10% patients were thrombocytopenia (22%), leucopenia (13%) and neutropenia (11%), respectively. Chidamide represents a novel oral benzamide class of HDAC inhibitor with significant single-agent activity and manageable toxicity in relapsed or refractory PTCL, and provides a much needed treatment option in this indication in China. Results led to China Food and Drug Administration approval of chidamide in this indication.

Shi Y ，Dong M ，Hong X ，Zhang W ，Feng J ，Zhu J ，Yu L ，Ke X ，Huang H ，Shen Z ，Fan Y ，Li W ，Zhao X ，Qi J ，Huang H ，Zhou D ，Ning Z ，Lu X ... -  《-》

Chidamide in relapsed or refractory peripheral T cell lymphoma: a multicenter real-world study in China.

Shi Y ，Jia B ，Xu W ，Li W ，Liu T ，Liu P ，Zhao W ，Zhang H ，Sun X ，Yang H ，Zhang X ，Jin J ，Jin Z ，Li Z ，Qiu L ，Dong M ，Huang X ，Luo Y ，Wang X ，Wang X ，Wu J ，Xu J ，Yi P ，Zhou J ，He H ，Liu L ，Shen J ，Tang X ，Wang J ，Yang J ，Zeng Q ，Zhang Z ，Cai Z ，Chen X ，Ding K ，Hou M ，Huang H ，Li X ，Liang R ，Liu Q ，Song Y ，Su H ，Gao Y ，Liu L ，Luo J ，Su L ，Sun Z ，Tan H ，Wang H ，Wang J ，Wang S ，Zhang H ，Zhang X ，Zhou D ，Bai O ，Wu G ，Zhang L ，Zhang Y ... -  《Journal of Hematology & Oncology》

Results from a pivotal, open-label, phase II study of romidepsin in relapsed or refractory peripheral T-cell lymphoma after prior systemic therapy.

Coiffier B ，Pro B ，Prince HM ，Foss F ，Sokol L ，Greenwood M ，Caballero D ，Borchmann P ，Morschhauser F ，Wilhelm M ，Pinter-Brown L ，Padmanabhan S ，Shustov A ，Nichols J ，Carroll S ，Balser J ，Balser B ，Horwitz S ... -  《-》

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

Rai S ，Kim WS ，Ando K ，Choi I ，Izutsu K ，Tsukamoto N ，Yokoyama M ，Tsukasaki K ，Kuroda J ，Ando J ，Hidaka M ，Koh Y ，Shibayama H ，Uchida T ，Yang DH ，Ishitsuka K ，Ishizawa K ，Kim JS ，Lee HG ，Minami H ，Eom HS ，Kurosawa M ，Lee JH ，Lee JS ，Lee WS ，Nagai H ，Shindo T ，Yoon DH ，Yoshida S ，Gillings M ，Onogi H ，Tobinai K ... -  《-》

Sintilimab (anti-PD-1 antibody) plus chidamide (histone deacetylase inhibitor) in relapsed or refractory extranodal natural killer T-cell lymphoma (SCENT): a phase Ib/II study.

Anti-PD-1 antibodies are a favorable treatment for relapsed or refractory extranodal natural killer T cell lymphoma (RR-ENKTL), however, the complete response (CR) rate and the duration of response (DOR) need to be improved. This phase 1b/2 study investigated the safety and efficacy of sintilimab, a fully human anti-PD-1 antibody, plus chidamide, an oral subtype-selective histone deacetylase inhibitor in 38 patients with RR-ENKTL. Expected objective response rate (ORR) of combination treatment was 80%. Patients received escalating doses of chidamide, administered concomitantly with fixed-dose sintilimab in 21-days cycles up to 12 months. No dose-limiting events were observed, RP2D of chidamide was 30 mg twice a week. Twenty-nine patients were enrolled in phase 2. In the intention-to-treat population (n = 37), overall response rate was 59.5% with a complete remission rate of 48.6%. The median DOR, progression-free survival (PFS), and overall survival (OS) were 25.3, 23.2, and 32.9 months, respectively. The most common grade 3 or higher treatment-emergent adverse events (AEs) were neutropenia (28.9%) and thrombocytopenia (10.5%), immune-related AEs were reported in 18 (47.3%) patients. Exploratory biomarker assessment suggested that a combination of dynamic plasma ctDNA and EBV-DNA played a vital prognostic role. STAT3 mutation shows an unfavorable prognosis. Although outcome of anticipate ORR was not achieved, sintilimab plus chidamide was shown to have a manageable safety profile and yielded encouraging CR rate and DOR in RR-ENKTL for the first time. It is a promising therapeutic option for this population.

Gao Y ，He H ，Li X ，Zhang L ，Xu W ，Feng R ，Li W ，Xiao Y ，Liu X ，Chen Y ，Wang X ，Bai B ，Wu H ，Cai Q ，Li Z ，Li J ，Lin S ，He Y ，Ping L ，Huang C ，Mao J ，Chen X ，Zhao B ，Huang H ... -  《-》