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.
J Clin Oncol. 2016 Oct 1;34(28):3426-33. doi: 10.1200/JCO.2016.67.8250. Epub 2016 Aug 9.
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.
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.
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.
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.
异基因造血干细胞移植（allo-HSCT）是侵袭性成人 T 细胞白血病/淋巴瘤（ATLL）患者的重要治疗选择之一。莫格珠单抗（抗 CCR4 单克隆抗体；莫格）最近在日本被批准用于治疗 ATLL。由于莫格在几个月内耗尽调节性 T 细胞，因此人们对移植前使用莫格可能产生的不良反应存在较大担忧。我们评估了 allo-HSCT 前使用莫格对移植后临床结局的影响。
我们纳入了 996 例年龄 70 岁及以下、诊断为侵袭性 ATLL 的 allo-HSCT 受者，这些患者在 2000 年至 2013 年间接受了包含多种化疗药物的强化化疗作为一线治疗。在 allo-HSCT 前，82 例患者接受了莫格治疗，最后一次莫格治疗与 allo-HSCT 的间隔中位数为 45 天。
allo-HSCT 前使用莫格与 3 级至 4 级急性移植物抗宿主病（GVHD；相对风险，1.80；P <.01）和急性 GVHD 对全身皮质类固醇抵抗（相对风险，2.09；P <.01）的风险增加相关。与未使用莫格的患者相比，allo-HSCT 前使用莫格的患者 1 年累积非复发死亡率显著更高（43.7%比 25.1%；P <.01）。与未使用莫格的患者相比，allo-HSCT 前使用莫格的患者 1 年总生存率也显著较低（32.3%比 49.4%；P <.01）。特别是，在 allo-HSCT 前使用莫格的间隔 < 50 天与较差的临床结局相关。
allo-HSCT 前使用莫格与 GVHD 相关死亡率增加显著相关，这支持了 CCR4 表达的 Tregs 在人类 allo-HSCT 后的相关性。在临床实践中，对于适合 allo-HSCT 的 ATLL 患者，应谨慎使用莫格。
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