Y Shi1, M Dong2, X Hong3, W Zhang4, J Feng5, J Zhu6, L Yu7, X Ke8, H Huang15, Z Shen10, Y Fan11, W Li12, X Zhao13, J Qi14, H Huang15, D Zhou16, Z Ning17, X Lu17. 1. Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing syuankai@cicams.ac.cn. 2. Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing. 3. Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai. 4. Department of Lymphoma, 307 Hospital of PLA, Beijing. 5. Department of Medical Oncology, Jiangsu Cancer Hospital, Nanjing. 6. Department of Medical Oncology, Beijing Caner Hospital, Beijing. 7. Department of Hematology, Chinese PLA General Hospital, Beijing. 8. Department of Hematology, Peking University Third Hospital, Beijing. 9. Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou. 10. Department of Hematology, Ruijin Hospital/Medical College, Shanghai Jiao Tong University, Shanghai. 11. Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou. 12. Department of Hematology, the First Hospital, Jilin University, Changchun. 13. Department of Hematology, Xiangya Hospital Central South University, Changsha. 14. Department of Lymphoma, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin. 15. Department of Hematology, the First Affiliated Hospital, Zhejiang University, Hangzhou. 16. Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing. 17. Chipscreen Biosciences Ltd, Shenzhen, China.
Abstract
BACKGROUND: 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 AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: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 AND METHODS: 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. RESULTS: 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. CONCLUSION: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.
Authors: Zhaoyun Liu; Jin Chen; Honglei Wang; Kai Ding; Yanqi Li; Anya de Silva; Varun Sehgal; Jonathan Lvan Burbano; Radhika Sundararaj; Janani Gamage; Victor Audu; Rong Fu Journal: Am J Transl Res Date: 2017-12-15 Impact factor: 4.060