Shigeo Fuji1, Yoshitaka Inoue2, Atae Utsunomiya2, Yukiyoshi Moriuchi2, Kaoru Uchimaru2, Ilseung Choi2, Eiichi Otsuka2, Hideho Henzan2, Koji Kato2, Takeaki Tomoyose2, Hisashi Yamamoto2, Saiko Kurosawa2, Ken-Ichi Matsuoka2, Takuhiro Yamaguchi2, Takahiro Fukuda2. 1. Shigeo Fuji, Yoshitaka Inoue, Saiko Kurosawa, and Takahiro Fukuda, National Cancer Center Hospital; Kaoru Uchimaru, The University of Tokyo; Hisashi Yamamoto, Toranomon Hospital, Tokyo; Yoshitaka Inoue, Kumamoto University Hospital, Kumamoto; Atae Utsunomiya, Imamura Bun-in Hospital, Kagoshima; Yukiyoshi Moriuchi, Sasebo City General Hospital, Sasebo; Ilseung Choi, National Hospital Organization Kyushu Cancer Center; Hideho Henzan, Hamanomachi Hospital; Koji Kato, Kyushu University Graduate School of Medical Sciences, Fukuoka; Eiichi Otsuka, Oita Prefectural Hospital, Oita; Takeaki Tomoyose, University of the Ryukyus, Okinawa; Ken-ichi Matsuoka, Okayama University, Okayama; and Takuhiro Yamaguchi, Tohoku University Graduate School of Medicine, Sendai, Japan. sfuji@ncc.go.jp. 2. Shigeo Fuji, Yoshitaka Inoue, Saiko Kurosawa, and Takahiro Fukuda, National Cancer Center Hospital; Kaoru Uchimaru, The University of Tokyo; Hisashi Yamamoto, Toranomon Hospital, Tokyo; Yoshitaka Inoue, Kumamoto University Hospital, Kumamoto; Atae Utsunomiya, Imamura Bun-in Hospital, Kagoshima; Yukiyoshi Moriuchi, Sasebo City General Hospital, Sasebo; Ilseung Choi, National Hospital Organization Kyushu Cancer Center; Hideho Henzan, Hamanomachi Hospital; Koji Kato, Kyushu University Graduate School of Medical Sciences, Fukuoka; Eiichi Otsuka, Oita Prefectural Hospital, Oita; Takeaki Tomoyose, University of the Ryukyus, Okinawa; Ken-ichi Matsuoka, Okayama University, Okayama; and Takuhiro Yamaguchi, Tohoku University Graduate School of Medicine, Sendai, Japan.
Abstract
PURPOSE: Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is one important treatment option for patients with aggressive adult T-cell leukemia/lymphoma (ATLL). Mogamulizumab (anti-CCR4 monoclonal antibody; Mog) was recently approved as a treatment for ATLL in Japan. Major concerns exist about the possible adverse effects of pretransplantation Mog because Mog depletes regulatory T cells for several months. We assessed the impact of pretransplantation Mog on clinical outcomes after allo-HSCT. PATIENTS AND METHODS: We included 996 allo-HSCT recipients age 70 years or younger with aggressive ATLL who were given the diagnosis between 2000 and 2013 and who received intensive chemotherapy by multiple chemotherapeutic drugs as first-line therapy. Before allo-HSCT, 82 patients received Mog with a median interval of 45 days from the last Mog to allo-HSCT. RESULTS: Pretransplantation Mog was associated with an increased risk of grade 3 to 4 acute graft-versus-host disease (GVHD; relative risk, 1.80; P < .01) and refractoriness to systemic corticosteroid for acute GVHD (relative risk, 2.09; P < .01). One-year cumulative incidence of nonrelapse mortality was significantly higher in patients with pretransplantation Mog compared with those without (43.7% v 25.1%; P < .01). The probability of 1-year overall survival was also significantly inferior in patients with pretransplantation Mog compared with those without (32.3% v 49.4%; P < .01). In particular, use of Mog with intervals < 50 days to allo-HSCT was associated with a dismal clinical outcome. CONCLUSION: Pretransplantation Mog was significantly associated with an increased risk of GVHD-related mortality, which supports the relevance of CCR4-expressing Tregs after allo-HSCT in humans. In clinical practice, Mog should be cautiously used for patients with ATLL who are eligible for allo-HSCT.
PURPOSE: Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is one important treatment option for patients with aggressive adult T-cell leukemia/lymphoma (ATLL). Mogamulizumab (anti-CCR4 monoclonal antibody; Mog) was recently approved as a treatment for ATLL in Japan. Major concerns exist about the possible adverse effects of pretransplantation Mog because Mog depletes regulatory T cells for several months. We assessed the impact of pretransplantation Mog on clinical outcomes after allo-HSCT. PATIENTS AND METHODS: We included 996 allo-HSCT recipients age 70 years or younger with aggressive ATLL who were given the diagnosis between 2000 and 2013 and who received intensive chemotherapy by multiple chemotherapeutic drugs as first-line therapy. Before allo-HSCT, 82 patients received Mog with a median interval of 45 days from the last Mog to allo-HSCT. RESULTS: Pretransplantation Mog was associated with an increased risk of grade 3 to 4 acute graft-versus-host disease (GVHD; relative risk, 1.80; P < .01) and refractoriness to systemic corticosteroid for acute GVHD (relative risk, 2.09; P < .01). One-year cumulative incidence of nonrelapse mortality was significantly higher in patients with pretransplantation Mog compared with those without (43.7% v 25.1%; P < .01). The probability of 1-year overall survival was also significantly inferior in patients with pretransplantation Mog compared with those without (32.3% v 49.4%; P < .01). In particular, use of Mog with intervals < 50 days to allo-HSCT was associated with a dismal clinical outcome. CONCLUSION: Pretransplantation Mog was significantly associated with an increased risk of GVHD-related mortality, which supports the relevance of CCR4-expressing Tregs after allo-HSCT in humans. In clinical practice, Mog should be cautiously used for patients with ATLL who are eligible for allo-HSCT.
Authors: Julia Dai; Timothy H Almazan; Eric K Hong; Michael S Khodadoust; Sally Arai; Wen-Kai Weng; Youn H Kim Journal: JAMA Dermatol Date: 2018-06-01 Impact factor: 10.282