Sugio Takeshi, Kato Koji, Aoki Takatoshi, Ohta Takanori, Saito Noriyuki, Yoshida Shuro, Kawano Ichiro, Henzan Hideho, Kadowaki Masanori, Takase Ken, Muta Tsuyoshi, Miyawaki Kohta, Yamauchi Takuji, Shima Takahiro, Takashima Shuichiro, Mori Yasuo, Yoshimoto Goichi, Kamezaki Kenjiro, Takenaka Katsuto, Iwasaki Hiromi, Ogawa Ryosuke, Ohno Yuju, Eto Tetsuya, Kamimura Tomohiko, Miyamoto Toshihiro, Akashi Koichi
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Biol Blood Marrow Transplant. 2016 Sep;22(9):1608-1614. doi: 10.1016/j.bbmt.2016.05.017. Epub 2016 May 21.
Mogamulizumab (MOG), a humanized anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, has recently played an important role in the treatment of adult T cell leukemia/lymphoma (ATLL). Because CCR4 is expressed on normal regulatory T cells as well as on ATLL cells, MOG may accelerate graft-versus-host disease (GVHD) by eradicating regulatory T cells in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, there is limited information about its safety and efficacy in patients treated with MOG before allo-HSCT. In the present study, 25 patients with ATLL were treated with MOG before allo-HSCT, after which 18 patients (72%) achieved remission. The overall survival and progression-free survival at 1 year post-transplantation were 20.2% (95% CI, 6.0% to 40.3%) and 15.0% (95% CI, 4.3% to 32.0%), respectively. The cumulative incidence of acute GVHD was 64.0% (95% CI, 40.7% to 80.1%) for grade II-IV and 34.7% (95% CI, 15.8% to 54.4%) for grade III-IV. The cumulative incidence of transplantation-related mortality (TRM) was 49.0% (95% CI, 27.0% to 67.8%). Six of 7 patients with acute GVHD grade III-IV died from GVHD, which was the leading cause of death. In particular, a shorter interval from the last administration of MOG to allo-HSCT was associated with more severe GVHD. MOG use before allo-HSCT may decrease the ATLL burden; however, it is associated with an increase in TRM due to severe GVHD. Because MOG is a potent anti-ATLL agent, new treatment protocols should be developed to integrate MOG at suitable doses and timing of administration to minimize unwanted GVHD development.
莫加穆单抗(MOG)是一种人源化抗CC趋化因子受体4(CCR4)单克隆抗体,最近在成人T细胞白血病/淋巴瘤(ATLL)的治疗中发挥了重要作用。由于CCR4在正常调节性T细胞以及ATLL细胞上均有表达,MOG可能通过清除异基因造血干细胞移植(allo-HSCT)患者的调节性T细胞来加速移植物抗宿主病(GVHD)。然而,关于其在allo-HSCT前接受MOG治疗患者中的安全性和疗效的信息有限。在本研究中,25例ATLL患者在allo-HSCT前接受了MOG治疗,其中18例(72%)实现缓解。移植后1年的总生存率和无进展生存率分别为20.2%(95%CI,6.0%至40.3%)和15.0%(95%CI,4.3%至32.0%)。II-IV级急性GVHD的累积发生率为64.0%(95%CI,40.7%至80.1%),III-IV级为34.7%(95%CI,15.8%至54.4%)。移植相关死亡率(TRM)的累积发生率为49.0%(95%CI,27.0%至67.8%)。7例III-IV级急性GVHD患者中有6例死于GVHD,这是主要死因。特别是,从最后一次给予MOG到allo-HSCT的间隔时间越短,GVHD越严重。allo-HSCT前使用MOG可能会减轻ATLL负担;然而,它与严重GVHD导致的TRM增加有关。由于MOG是一种有效的抗ATLL药物,应制定新的治疗方案,以在合适的剂量和给药时间整合MOG,以尽量减少不必要的GVHD发生。