Pretransplantation anti-CCR4 antibody mogamulizumab against adult T-cell leukemia/lymphoma is associated with significantly increased risks of severe and corticosteroid-refractory graft-versus-host disease, nonrelapse mortality, and overall mortality

Shigeo Fuji, Yoshitaka Inoue, Atae Utsunomiya, Yukiyoshi Moriuchi, Kaoru Uchimaru, Ilseung Choi, Eiichi Otsuka, Hideho Henzan, Koji Kato, Takeaki Tomoyose, Hisashi Yamamoto, Saiko Kurosawa, Ken Ichi Matsuoka, Takuhiro Yamaguchi, Takahiro Fukuda

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    66 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)3426-3433
    Number of pages8
    JournalJournal of Clinical Oncology
    Volume34
    Issue number28
    DOIs
    Publication statusPublished - Oct 1 2016

    All Science Journal Classification (ASJC) codes

    • Oncology
    • Cancer Research

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