Impact of Mogamulizumab-Containing Chemotherapy on HBV Reactivation in Patients with T-Cell Lymphoma: A Multicenter Retrospective Observational Study (PROACTIVE-MOGA)

Abstract

INTRODUCTION Reactivation of hepatitis B virus (HBV) infection is a potentially lethal complication, but may be preventable in patients with chronic HBV infection or resolved HBV infection who receive systemic chemotherapy.The risk of HBV reactivation (HBVR) depends on not only HBV infectious status but also type of systemic chemotherapy. An anti-CCR4 antibody, mogamulizumab (Moga), has been developed for the treatment of peripheral T-cell lymphomas. Moga is known to suppress CCR4-positive regulatory T cells and helper T cells, which can lead to immunological dysfunction. However, there is little evidence regarding the risk of HBVR in patients with chronic HBV infection or resolved HBV infection who receive Moga-containing systemic chemotherapy. We conducted a retrospective observational study to evaluate the risk of HBVR and clinical outcome in those patients. METHODS & MATERIALS: Patients treated with Moga-containing chemotherapy for T-cell lymphoma between May 2012 and March 2021, who were chronic HBV infection (defined as seropositive for HBsAg) or resolved HBV infection (defined as seronegative for HBsAg, but seropositive for anti-HBc or anti-HBs), were included. The primary endpoint was the rate of HBVR; HBVR in HBsAg-positive patients was defined as any of the following three criteria: 1) 2 log or more increase in HBV DNA from baseline, 2) 3.0 Log IU/ml or more of HBV DNA in patients with undetectable HBV DNA at baseline, 3) 4.0 Log IU/ml or more of HBV DNA in patients not available for HBV DNA at baseline. HBVR in HBsAg-negative patients was defined as any of following three criteria: 1) detectable for HBV DNA in patients with undetectable HBV DNA at baseline, 2) 1.3 Log IU/mL or more of HBV DNA in patients not available for HBV DNA at baseline, 3) seroconversion of HBsAg. RESULTS: A total of 23 HBsAg-positive patients and 246 resolved HBV-infected patients were retrospectively reviewed. Among the 23 HBsAg-positive patients, the median age was 65 years (interquartile range [IQR], 63-73) and 19 patients (82%) had adult T-cell leukemia-lymphoma (ATL). Baseline HBV DNA was undetectable level, detectable not quantifiable, and detectable in 9 (39%), 2 (9%), and 12 (52%) patients, respectively. All 23 HBsAg-positive patients received anti-HBV prophylaxis prior to Moga treatment. One of 23 (4.3%) patients experienced HBVR who led to HBV-related hepatitis. Among the 241 patients with resolved HBV infection, the median age was 65 years (IQR, 63-73) and 223 patients (91%) had ATL. Baseline serostatus of anti-HBc and anti-HBs were as follows: anti-HBc positive and anti-HBs positive in 177 patients (72%), anti-HBc-positive but anti-HBs negative in 50 (20%), the remaining 9 were anti-HBc negative but anti-HBs positive. Baseline HBV DNA was undetectable in 233 (95%), detectable not quantifiable in 5 (2%), and the remaining 3 were detectable for HBV DNA. Only 3 patients received anti-HBV prophylaxis. HBVR occurred in 11 patients, and the 2-year cumulative HBVR rate was 3.5% (95% CI, 1.6-16.5). Among the 11 patients with HBVR, the median peak HBV DNA level was 2.1 Log IU/mL (IQR, 1.7-5.0), the median time from first dose of Moga to HBVR was 140 days (IQR, 82-765) and 2 had HBV-related hepatitis. CONCLUSION: Our current study showed that the risk of HBVR was 4.3% (1 of 23) among HBsAg-positive patients with antiviral prophylaxis and 4.6% (11 of 238) among resolved HBV-infected patients without antiviral prophylaxis following Moga-containing chemotherapy. Anti-HBV prophylaxis and HBV DNA monitoring guided preemptive anti-HBV therapy are recommended to prevent HBV-related hepatitis for HBsAg-positive and resolve HBV-infected patients, respectively.