Hepatitis B (HBV) Screening in Patients Receiving Rituximab: A Comprehensive Analysis Including Comparison of Adherence By Oncologists and Non-Oncologists
Authors: Puri Aditi , Stevenson Ryan L. , Khouri Jack , Comenzo Raymond L. , Kao Grace Shih-Hui , Klein Andreas K. , Miller Kenneth B. , Rosenberg Aaron , Smith Hedy , Sprague Kellie A. , Relias Valerie , Evens Andrew M. 
Published: November 2019

Abstract
BACKGROUND: It is estimated that >1.4 million people in the US are living with chronic HBV, many of whom are unaware of their infection. Chronic infection is responsible for the majority of HBV-related morbidity and mortality ranging from hepatitis to fulminant hepatic failure. The monoclonal anti-CD20 antibody, rituximab, is used to treat a variety of malignant and non-malignant conditions. Its use is associated with reactivation of HBV (HBV-R), including in historically low risk populations (i.e., HBV core antibody (HBcAb) positivity) and HBV-R may occur >8-10 months after completion of therapy. Professional societies such as the CDC and Infectious Diseases Society of America (IDSA) recommend screening all persons receiving cytotoxic or immunosuppressive therapy for HBV infection, although not all guidelines surrounding this topic are consistent. The primary aim of this study was to determine the rate of rituximab-related HBV screening and HBV-R over a recent time period across multiple medical specialties and disease conditions.
METHODS: We completed a single center, retrospective cohort study at an urban, academic medical center reviewing all patients (pts) ≥ 18 years of age who received rituximab 1/1/06 to 7/31/13 who had at least 12 months of follow-up following the final rituximab dose. Eligible pts were queried using an electronic pharmacy database and reviewed by 3 physicians. Detailed data included demographics, indication for rituximab, number of rituximab doses, HBV screening serology, vaccination status, and comorbidities and risk factors for HBV-R.
RESULTS: We identified 407 pts; of these, 10 were excluded due inadequate follow-up, 7 for incomplete records, and 1 was due to age <18 years with 389 pts meeting inclusion criteria. 47% of pts were female and the median age was 63 years (range, 19-94 years). The median number of rituximab doses received was 5 (1-35) and 86% of pts had a hematologic or oncologic diagnosis (most common: DLBCL n=84, CLL n=49, follicular lymphoma n=35, marginal zone lymphoma n=17, mantle cell lymphoma n=15, acute leukemia n=14, myeloma/amyloid n=13, ITP n=12, hemolytic anemia, n=10 and Burkitt’s n=9) and 14% of pts had a non-oncology indication (most common: rheumatoid arthritis n=20, lupus n=5, vasculitits n=4, scleritis n=3, Wegner’s n=3, Sjogren’s n=3, and dermatomyositis n=3) for rituximab therapy. Overall, 32% of pts were screened for HBV <6 months prior to the 1st rituximab dose. Among hematology/oncology pts, 31% had HBV screening prior to rituximab with 24% occurring within 6 months prior to the 1st dose (3% 6-12 months, 3% 12-24 months, and 1% >24 months prior). For non-oncology pts, 40% had HBV screening with 26% occurring within 6 months prior to the 1st dose (6% 6-12 months, 2%, 12-24 months, and 6% >24 months prior). Interestingly, the type of HBV screening tests varied widely with no consistent panel of serologies tested, although the majority of pts who had screening had testing for HBV surface antigen (90.7%). HBcAb was not checked as often (66%), which represents a subset of pts at risk for developing HBV-R. Of pts screened for HBcAb, 15/88 (17%) were found to be positive for HBV (n=14 HBcAb and n=1 pt was positive for HBV surface antigen). 8/15 pts had no known or obvious risk factors for HBV infection. Of the 14 pts testing positive for HBcAb prior to rituximab, only 1 pt received anti-HBV prophylactic therapy. 3 of 14 pts without HBV prophylaxis experienced HBV-R (all HBcAb+ lymphoma pts treated with rituximab/chemotherapy), one of who died due to multiorgan failure.
CONCLUSION: At our academic center, we identified a relatively low rate of HBV screening amongst pts receiving rituximab irrespective of disease specialist or diagnostic condition. In addition, among pts who were screened, testing panels were inconsistent and a significant minority of pts did not have testing for HBcAb. Furthermore, we identified a relatively high rate of occult positivity for HBcAb including in a significant fraction of pts without known risk factors. It is advocated that a National unified guideline be instituted towards rituximab-related HBV screening and institutions implement and adhere to these guidelines. Likewise, a standardized panel of HBV serology is essential, both for initial testing and follow up. This is especially important given the increasing number of FDA approvals of other anti-CD20 and related monoclonal antibodies that carry similar risks of HBV-R.

Disclosures
Evens: Genentech: Honoraria, Speakers Bureau.