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

• Published in: Signal transduction and targeted therapy Vol. 9; no. 1; p. 121
• Main Authors: Gao, Yan, He, Haixia, Li, Xueping, Zhang, Liling, Xu, Wei, Feng, Ru, Li, Wenyu, Xiao, Yin, Liu, Xinxiu, Chen, Yu, Wang, Xiaoxiao, Bai, Bing, Wu, Huijing, Cai, Qingqing, Li, Zhiming, Li, Jibin, Lin, Suxia, He, Yanxia, Ping, Liqin, Huang, Cheng, Mao, Jiaying, Chen, Xiujin, Zhao, Baitian, Huang, Huiqiang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.05.2024; Nature Publishing Group
• Subjects: 692/308/2779/109; 692/4028/67/1990; 692/53/2423; Adult; Aged; Aminopyridines - administration & dosage; Aminopyridines - adverse effects; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Benzamides - administration & dosage; Benzamides - adverse effects; Benzamides - therapeutic use; Cancer Research; Cell Biology; Female; Histone deacetylase; Histone Deacetylase Inhibitors - administration & dosage; Histone Deacetylase Inhibitors - adverse effects; Histone Deacetylase Inhibitors - therapeutic use; Humans; Internal Medicine; Lymphocytes T; Lymphoma; Lymphoma, Extranodal NK-T-Cell - drug therapy; Lymphoma, Extranodal NK-T-Cell - pathology; Male; Medical prognosis; Medicine; Medicine & Public Health; Middle Aged; Natural killer cells; Neutropenia; Oncology; Pathology; PD-1 protein; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Programmed Cell Death 1 Receptor - immunology; Remission; Response rates; Stat3 protein; T-cell lymphoma; Thrombocytopenia
• ISSN: 2059-3635; 2095-9907; 2059-3635
• DOI: 10.1038/s41392-024-01825-0

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.