Hepatitis B Virus (HBV) Screening and Associated Outcomes in Malignant Hematology Patients Receiving Rituximab Therapy within the Rossy Cancer Network
Authors: Li Shen , Ali Allaa , Lawandi Alexander , Fernandez Myriam , Rousseau Caroline , Thomas Doneal , Assouline Sarit , Cassis Chantal , Lee Todd Campbell , Davison Kelly L. 
Published: October 2019

Abstract
Introduction. Hepatitis B Virus (HBV) reactivation is an important risk of Rituximab therapy, a potent immunosuppressant used as part of chemotherapy regimens against non-Hodgkin's lymphoma. HBV reactivation is a potentially fatal complication that can be largely prevented with antiviral prophylaxis and monitoring of HBV DNA. American Society of Clinical Oncology (ASCO) 2015 guidelines recommend that all patients be screened for both hepatitis B core antibody (anti-HBc) and surface antigen (HBsAg) before initiating Rituximab therapy. According to ASCO, the rates of screening for non-Hodgkin's lymphoma patients before the administration of Rituximab were less than 70% in 2014 for US centers participating in ASCO's Quality Oncology Practice Initiative. A 2014/15 study at the McGill University Health Centre found that about a third of patients were inadequately screened (A Lawandi, et al).
Methods. The objective of this retrospective study was to assess the quality of HBV screening and monitoring at the partner hospitals of the Rossy Cancer Network (RCN). From the pharmacy database of the Jewish General Hospital, McGill University Health Centre, and St. Mary's Hospital Center, we obtained the set of patients with hematologic malignancies who began Rituximab treatment between April 2014 and March 2016. We then collected laboratory data on the screening of anti-HBc and HBsAg. Screening was considered appropriate if performed for both anti-HBc and HBsAg in the 6-month window preceding Rituximab administration and considered suboptimal if patients were tested outside this time frame, or for only one of the two tests. Additionally, patient chart reviews were used to collect follow-up information and outcomes for screened patients. Follow-up was considered appropriate when anti-viral treatment was given for infected patients and when patients at risk for reactivation received prophylactic treatment or HBV DNA monitoring.
Results. Four hundred and seventy-four patients initiated Rituximab-containing treatment. Of those, 213 (45%) met the criteria for appropriate HBV screening and 138 (29%) for suboptimal screening. Of the patients that were screened (N=351), 6 were actively infected (HBsAg+/ anti-HBc+) and 41 were at risk for reactivation (HBsAg-/ anti-HBc+). All actively infected patients received antiviral treatment as per ASCO guidelines but only 18 (44%) of patients at risk for reactivation received appropriate follow-up, prophylactic treatment or HBV DNA monitoring. HBV reactivation was noted in 2 patients, one of whom died of a hepatic flare.
Conclusion. Between 2014 and 2016, less than 50% of Rituximab-treated hematologic cancer patients within the RCN partnered hospitals were appropriately screened for HBV, and 44% of patients at risk for reactivation received appropriate follow-up. In response to these findings, the RCN Hematology Disease Site Group is developing RCN clinical practice guidelines to standardize HBV testing and management of patients at-risk for HBV reactivation. In close collaboration with virologists and hepatologists, the group will provide targeted education sessions to improve compliance with clinical practice guidelines. Additionally, the group aims to implement pharmacy-based interventions, such as coupling Rituximab prescriptions with standard orders for HBV testing, and providing pharmacist autonomy to order HBV testing.

Disclosures
Assouline: Novartis: Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Honoraria, Research Funding, Speakers Bureau; Pfizer: Honoraria, Research Funding, Speakers Bureau; Roche: Honoraria, Research Funding, Speakers Bureau.