Elucidation of mechanism of HBV reactivation associated with mogamulizumab-containing chemotherapy

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K09876
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Nagoya City University
• Principal Investigator: Kusumoto Shigeru 名古屋市立大学, 医薬学総合研究院(医学), 准教授 (90423855)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: モガムリズマブ / HBV再活性化 / 免疫不全

Outline of Final Research Achievements

The risk of hepatitis B virus reactivation (HBV-R) in adult T-cell leukemia-lymphoma (ATL) patients with resolved HBV infection treated with mogamulizumab (MOGA) was analyzed in a post hoc analysis.Of 102 patients with ATL who were enrolled in a multicenter prospective observational study (MIMOGA study;UMIN000008696), 39 (38%) had resolved HBV infection based on the serological results at each institute. Of these 39 patients , 34 who underwent periodic HBV DNA monitoring at least once after enrollment were included in this study. HBV-R was defined as HBV DNA levels of 1.3 log IU/mL or more. With a median HBV DNA follow-up period of 467 days, HBV-R was observed in three patients, one of which developed HBV-related hepatitis. The incidence of resolved HBV infection was 38%, while HBV-R following MOGA administration, including one case with HBV-R that developed after umbilical cord blood transplantation, occurred in approximately 9% (3 of 34 patients) in the MIMOGA study.

Free Research Field

血液・腫瘍内科学

Academic Significance and Societal Importance of the Research Achievements

CCR4抗体モガムリズマブは、難治性の成人T細胞白血病リンパ腫（ATL）治療において高い有効性が報告されてきたが、末梢血中に存在する正常のCD4リンパ球の一部を除去することによる免疫不全がB型肝炎ウイルス（HBV）の再活性化と関連することが本研究によって示された。日本肝臓学会が提唱するガイドラインに従い、定期的なHBV DNAモニタリングにより早期にHBV再活性化を診断し、適切なタイミングで核酸アナログを投与することで、HBV既往感染歴を有するATL治療が安全に実施可能であることが示された。同種移植後の免疫再構築による遅発発症のHBV再活性化例への対策は今後の課題と考えられた。