Ting Zhang1,2, Jing Sun3, Jinying Li4, Yunuo Zhao1,2, Tao Zhang1,2, Ruoning Yang1,2, Xuelei Ma5. 1. Department of Biotherapy, State Key Laboratory of Biotherapy, West China Hospital, Cancer Center, Sichuan University, No. 37 Guo Xue Alley, Chengdu, 610041, Sichuan, China. 2. West China Hospital, West China School of Medicine, Sichuan University, Chengdu, China. 3. Qingdao central hospital, Qingdao University, Qingdao, Shandong, China. 4. Department of radiotherapy, Qingdao central hospital, Qingdao University, Qingdao, Shandong, China. 5. Department of Biotherapy, State Key Laboratory of Biotherapy, West China Hospital, Cancer Center, Sichuan University, No. 37 Guo Xue Alley, Chengdu, 610041, Sichuan, China. drmaxuelei@gmail.com.
Abstract
BACKGROUND: CC chemokine receptor 4 (CCR4), the receptor for CCL22 and CCL17, is expressed on the surface of effector Tregs that have the highest suppressive effects on antitumor immune response. CCR4 is also widely expressed on the surface of tumor cells from patients with adult T-cell leukemia/lymphoma (ATL), peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL). Mogamulizumab is a humanized, IgG1 kappa monoclonal antibody that is directed against CCR4. By reducing the number of CCR4-positive Tregs and tumor cells, the mogamulizumab can reduce tumor burden and boost antitumor immunity to achieve antitumor effects. METHODS: We examined the PubMed and ClinicalTrials.gov until 1 February 2020. Considering variability in different studies, we selected the adverse events (AEs), overall survival (OS), progression-free survival (PFS), objective responses rate (ORR) and Hazard Ratio (HR) for PFS to evaluate the safety and efficacy profile of mogamulizumab. RESULTS: When patients were treated with mogamulizumab monotherapy, the most common all-grade AEs were lymphopenia, infusion reaction, fever, rash and chills while the most common grade ≥ 3 AEs were lymphopenia, neutropenia and rash. When patients were treated with combined therapy of mogamulizumab and other drugs, the most common all-grade AEs were neutropenia, anaemia, lymphopenia and gastrointestinal disorder, while the most common grade ≥ 3 AEs was lymphopenia. For patients treated with mogamulizumab monotherapy, the pooled ORR and mean PFS were 0.430 (95% CI: 0.393-0.469) and 1.060 months (95% CI: 1.043-1.077), respectively. For patients treated with combined therapy of mogamulizumab and other drugs, the pooled ORR was 0.203 (95% CI: 0.022-0.746) while the pooled PFS and OS were 2.093 months (95% CI: 1.602-2.584) and 6.591 months (95% CI: 6.014-7.167), respectively. CONCLUSIONS: Based on present evidence, we believed that mogamulizumab had clinically meaningful antitumor activity with acceptable toxicity which is a novel therapy in treating patients with cancers.
BACKGROUND:CC chemokine receptor 4 (CCR4), the receptor for CCL22 and CCL17, is expressed on the surface of effector Tregs that have the highest suppressive effects on antitumor immune response. CCR4 is also widely expressed on the surface of tumor cells from patients with adult T-cell leukemia/lymphoma (ATL), peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL). Mogamulizumab is a humanized, IgG1 kappa monoclonal antibody that is directed against CCR4. By reducing the number of CCR4-positive Tregs and tumor cells, the mogamulizumab can reduce tumor burden and boost antitumor immunity to achieve antitumor effects. METHODS: We examined the PubMed and ClinicalTrials.gov until 1 February 2020. Considering variability in different studies, we selected the adverse events (AEs), overall survival (OS), progression-free survival (PFS), objective responses rate (ORR) and Hazard Ratio (HR) for PFS to evaluate the safety and efficacy profile of mogamulizumab. RESULTS: When patients were treated with mogamulizumab monotherapy, the most common all-grade AEs were lymphopenia, infusion reaction, fever, rash and chills while the most common grade ≥ 3 AEs were lymphopenia, neutropenia and rash. When patients were treated with combined therapy of mogamulizumab and other drugs, the most common all-grade AEs were neutropenia, anaemia, lymphopenia and gastrointestinal disorder, while the most common grade ≥ 3 AEs was lymphopenia. For patients treated with mogamulizumab monotherapy, the pooled ORR and mean PFS were 0.430 (95% CI: 0.393-0.469) and 1.060 months (95% CI: 1.043-1.077), respectively. For patients treated with combined therapy of mogamulizumab and other drugs, the pooled ORR was 0.203 (95% CI: 0.022-0.746) while the pooled PFS and OS were 2.093 months (95% CI: 1.602-2.584) and 6.591 months (95% CI: 6.014-7.167), respectively. CONCLUSIONS: Based on present evidence, we believed that mogamulizumab had clinically meaningful antitumor activity with acceptable toxicity which is a novel therapy in treating patients with cancers.
Authors: Yvette L Kasamon; Haiyan Chen; R Angelo de Claro; Lei Nie; Jingjing Ye; Gideon M Blumenthal; Ann T Farrell; Richard Pazdur Journal: Clin Cancer Res Date: 2019-07-31 Impact factor: 12.531
Authors: Madeleine Duvic; Lauren C Pinter-Brown; Francine M Foss; Lubomir Sokol; Jeffrey L Jorgensen; Pramoda Challagundla; Karen M Dwyer; Xiaoping Zhang; Michael R Kurman; Rocco Ballerini; Li Liu; Youn H Kim Journal: Blood Date: 2015-01-20 Impact factor: 22.113
Authors: Youn H Kim; Martine Bagot; Lauren Pinter-Brown; Alain H Rook; Pierluigi Porcu; Steven M Horwitz; Sean Whittaker; Yoshiki Tokura; Maarten Vermeer; Pier Luigi Zinzani; Lubomir Sokol; Stephen Morris; Ellen J Kim; Pablo L Ortiz-Romero; Herbert Eradat; Julia Scarisbrick; Athanasios Tsianakas; Craig Elmets; Stephane Dalle; David C Fisher; Ahmad Halwani; Brian Poligone; John Greer; Maria Teresa Fierro; Amit Khot; Alison J Moskowitz; Amy Musiek; Andrei Shustov; Barbara Pro; Larisa J Geskin; Karen Dwyer; Junji Moriya; Mollie Leoni; Jeffrey S Humphrey; Stacie Hudgens; Dmitri O Grebennik; Kensei Tobinai; Madeleine Duvic Journal: Lancet Oncol Date: 2018-08-09 Impact factor: 41.316