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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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

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Adult T Cell Leukemia Lymphoma
Hematopoietic Stem Cell Transplantation
Graft vs Host Disease
Anti-Idiotypic Antibodies
Adrenal Cortex Hormones
Mortality
mogamulizumab
Regulatory T-Lymphocytes
Japan
Therapeutics
Monoclonal Antibodies
Drug Therapy
Survival
Incidence

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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

In: Journal of Clinical Oncology, Vol. 34, No. 28, 01.10.2016, p. 3426-3433.

Research output: Contribution to journalArticle

Fuji, Shigeo ; Inoue, Yoshitaka ; Utsunomiya, Atae ; Moriuchi, Yukiyoshi ; Uchimaru, Kaoru ; Choi, Ilseung ; Otsuka, Eiichi ; Henzan, Hideho ; Kato, Koji ; Tomoyose, Takeaki ; Yamamoto, Hisashi ; Kurosawa, Saiko ; Matsuoka, Ken-ichi ; Yamaguchi, Takuhiro ; Fukuda, Takahiro. / 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. In: Journal of Clinical Oncology. 2016 ; Vol. 34, No. 28. pp. 3426-3433.
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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.",
author = "Shigeo Fuji and Yoshitaka Inoue and Atae Utsunomiya and Yukiyoshi Moriuchi and Kaoru Uchimaru and Ilseung Choi and Eiichi Otsuka and Hideho Henzan and Koji Kato and Takeaki Tomoyose and Hisashi Yamamoto and Saiko Kurosawa and Ken-ichi Matsuoka and Takuhiro Yamaguchi and Takahiro Fukuda",
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T1 - 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

AU - Fuji, Shigeo

AU - Inoue, Yoshitaka

AU - Utsunomiya, Atae

AU - Moriuchi, Yukiyoshi

AU - Uchimaru, Kaoru

AU - Choi, Ilseung

AU - Otsuka, Eiichi

AU - Henzan, Hideho

AU - Kato, Koji

AU - Tomoyose, Takeaki

AU - Yamamoto, Hisashi

AU - Kurosawa, Saiko

AU - Matsuoka, Ken-ichi

AU - Yamaguchi, Takuhiro

AU - Fukuda, Takahiro

PY - 2016/10/1

Y1 - 2016/10/1

N2 - 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.

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