Prediction of the risk for graft versus host disease after allogeneic hematopoietic stem cell transplantation in patients treated with mogamulizumab

Abstract

Mogamulizumab (Mog), an anti-C-C motif chemokine receptor 4 (CCR4) antibody, is a therapeutic for adult T-cell leukemia/lymphoma (ATL). Injuries of normal regulatory T cells (Tregs) which express CCR4 by Mog could result in immune-related adverse events including graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this study, we retrospectively analyzed 25 patients among 39 patients with ATL who received allo-HSCT. We found that the risk of grade II to IV GVHD was higher in patients who received Mog before or after allo-HSCT (Mog+) than in those who did not (Mog−). The incidence of severe intestinal GVHD and cytomegalovirus (CMV) enteritis were significantly higher in Mog + patients and resulted in death from GVHD or CMV enteritis. Treg numbers were suppressed until Mog serum concentrations became undetectable. Measuring the concentration of Mog and/or the number of Tregs at the time of allo-HSCT might predict the risk of GVHD.

Keywords:

• ATL
• allogeneic hematopoietic stem cell transplantation
• mogamulizumab
• GVHD
• regulatory T cell

Authors contribution

Contributions: YK analyzed the data and wrote the paper. YK, NA, MH, and DN collected and provided the patient samples. YK, MY, and KI designed the research.

Disclosure statement

KI reports receiving personal fees from Celgene, grants and personal fees from Kyowa Hakko Kirin, personal fees from Bristol-Myers Squibb, grants and personal fees from Chugai Pharmaceutical, grants and personal fees from Takeda Pharmaceutical, personal fees from Mundiharma, grants and personal fees from Taiho Pharmaceutical, personal fees from Janssen Pharmaceutical, personal fees from Novartis, personal fees from Pfizer, grants and personal fees from Astellas Pharma, personal fees from Genzyme, grants and personal fees from Sumitomo Dainippon Pharma, grants and personal fees from Eisai, grants and personal fees from Mochida, personal fees from Shire, personal fees from Otsuka Pharmaceutical, grants and personal fees from Ono Pharmaceutical, grants from Teijin Pharma, grants from Merck Sharp & Dohme Corp, grants from Asahi Kasei, grants from Eli Lilly, personal fees from Daiichi Sankyo, and personal fees from Huya Japan. The remaining authors declare no competing financial interests.