Hepatitis B Reactivation in Patients with Previous Hepatitis B Virus Exposure Undergoing Rituximab-Containing Chemotherapy for Lymphoma A Prospective Study

SUMMARY:The Centers for Disease Control and Prevention (CDC) estimates that there are 800,000 -1.4 million individuals with Chronic Hepatitis B infection in the United States. Reactivation of HBV is a major concern in cancer patients who may be on chemotherapy or other immunosuppressive therapies, with the incidence of HBV reactivation ranging from 40%-60% in those who are positive for Hepatitis B surface antigen (HBsAg). HBV reactivation is preventable with prophylactic antiviral therapy, failing which it can result in delays in cancer treatment as well as potentially fatal outcomes. The CDC updated their recommendations in 2008 and recommended HBV screening for patients receiving cytotoxic chemotherapy or immunotherapy. The American Society of Clinical Oncology in 2010 rendered a Provisional Clinical Opinion (PCO) suggesting that there was insufficient evidence to recommend routine screening for HBV in cancer patients, but screening may be considered for patient populations at high risk or for those who are to receive highly immunosuppressive therapies including anti-CD20 monoclonal antibody therapy such as RITUXAN® (Rituximab). According to the International recommendations, HBV reactivation is defined as the detection of serum HBV DNA of 10 IU/mL or more, by a real-time polymerase chain reaction–based assay. Because of the ambiguity regarding HBV reactivation in lymphoma patients receiving immunosuppressive therapy, the authors conducted a prospective trial to determine the frequency and factors predictive of HBV reactivation in HBsAg-negative, anti-HBc–positive patients treated with RITUXAN® based chemotherapy regimens. In this observational study, 260 patients with hematologic malignancies who were HBsAg-negative, anti-HBc–positive, with undetectable serum HBV DNA (< 10 IU/mL) and treated with RITUXAN® containing chemotherapy, were prospectively monitored every 4 weeks for up to 2 years. Patients were started on BARACLUDE® (Entecavir), when HBV reactivation (serum HBV DNA of 10 IU/mL or more), was documented. The cumulative rate of HBV reactivation over the 2 year observation period was high at 41.5%. The HBV reactivation occurred at a median of 23 weeks after RITUXAN® treatment and the median HBV DNA level at reactivation was 43 IU/mL. Undetectable antibody level to HBsAg (anti-HBs; < 10 mIU/mL) at baseline, prior to treatment with RITUXAN®, was the only significant risk factor that was strongly associated with HBV reactivation (P=0.009). Patients with negative baseline antibody level to HBsAg (anti-HBs) had a significantly higher 2-year cumulative rate of HBV reactivation, compared with those who had positive baseline antibody level to HBsAg (68.3% vs 34.4%; P=0.012). All patients had normal ALT when HBV reactivation occurred and except for one patient, were HBsAg negative. More importantly, all patients with HBV reactivation were successfully treated with BARACLUDE®. The authors concluded that HBsAg-negative, anti-HBc–positive lymphoma patients, receiving RITUXAN® based chemotherapy regimens experience a high rate of HBV reactivation, with this rate even significantly higher in patients with negative baseline antibody level to HBsAg. Periodic monitoring for HBV reactivation can enable early detection and intervention,thereby avoiding HBV related morbidities and mortality. Seto W, Chan T, Hwang Y, et al. JCO 2014;32:3736-3743