Hepatitis B Virus (HBV) Screening in Hematology/Oncology Patients Who Receive Rituximab: Continued Need for Evidence-Based Standardized Recommendations and Effective Implementation Into Clinical Practice

Abstract 970 Background: The CD20 monoclonal antibody, rituximab, has been implicated in the reactivation of hepatitis B virus (HBV) when given either combined with chemotherapy or as a single-agent. This potentially fatal complication has been documented in patients (pts) with high risk of HBV reactivation (i.e., HBV surface antigen (HBSAg) positive), and in lower risk populations (i.e., HBsAg negative, HBV core antibody (HBcAb) positive), the latter where the risk of reactivation with rituximab-based therapy is approximately 15–20% (Yeo W, et al. J Clin Oncol 2009; Evens AM et al, Ann Onc 2011). Published recommendations on HBV screening and anti-viral prophylaxis related to rituximab vary considerably, leaving practicing clinicians without clear consensus. In addition, HBV screening and prophylaxis have not been universally implemented into clinical practice. We sought to determine our institutional frequency of HBV screening and rates of HBV reactivation in Hematology/Oncology pts treated with rituximab-based therapy who underwent appropriate screening and prophylaxis. METHODS: We completed a single center, retrospective analysis at a large academic center to examine pts >17 years of age who received rituximab for a hematologic or oncologic disorder from January 1, 2005 through August 1, 2011. We reviewed drug administration records to identify pts who received rituximab for a malignancy or other hematological disorder. Pts were evaluated for documented HBV screening, HBV diagnosis, number of doses of rituximab received, vaccination status, baseline characteristics, and relevant past medical history and laboratory values. A ‘cycle’ of rituximab was defined as 1 dose given in combination with chemotherapy, 4 consecutive weeks given as a single agent, or 1 dose given q2-4 months as part of maintenance therapy. Data regarding use of prophylactic therapy for HBV were also collected. RESULTS: 212 pts were identified as having received rituximab; 109 were excluded as they received rituximab for other indications (n=86 multiple sclerosis, n=11 rheumatoid arthritis, and n=17 other), leaving a total of 103 pts who met study inclusion criteria. The median age was 63 years (19-90), median number of rituximab ‘cycles’ received was 3 (1-9); 45% of pts had diffuse large B-cell lymphoma (DLBCL), 15% other high-grade lymphoma, 14% follicular lymphoma (FL), and 26% other hematologic malignancy. Among the 103 pts, a total of 53 (51.4%) were screened for HBV at some point before or after initiation of therapy. Only 6.8% of pts were screened (within 9 months) prior to initiation of treatment, while 18.4% had HBV screening within 30 days of the 1st rituximab dose. Of the pts screened for HBV after 30 days, the median time to screening was 196 days (32-2660) after rituximab initiation. Notably, there were no differences in rates of HBV screening based on the year of therapy. Among the 53 pts screened for HBV prior to or within 30 days of rituximab initiation, eight (15.1%) were positive for HBV infection. Three pts were positive for HBsAg, all of whom received HBV anti-viral prophylaxis. Five pts were negative for HBsAg, but positive for HBcAb (1/5 also with positive HBV surface antibody); one HBcAb+ pt received anti-viral prophylaxis. These four pts received anti-viral prophylaxis for a median time of 17.1 months, which included a median of 7.9 months after the last rituximab dose. Among the 53 pts who underwent HBV screening, there were no cases of HBV reactivation observed with a median follow-up time of 15.6 months (5.9-16.5). CONCLUSION: At our academic institution, we identified an occult HBV infection rate of 15% in Hematology/Oncology pts who received rituximab treatment. A relatively low rate of pre-treatment HBV screening was performed, while approximately 45% of pts had screening after initiation of therapy. Among pts who were screened, appropriate anti-viral prophylaxis was instituted, and there were no cases of HBV reactivation. Altogether, there remains a critical need for standardized recommendations and consensus for screening and prophylaxis of HBV infection in pts who receive rituximab therapy. This is particularly evident given recent data regarding cost effectiveness of this approach (Zurawaska U, et al, J Clin Oncol 2012). In addition, continued efforts are needed to implement evidence-based HBV screening and prophylaxis guidelines in clinical practice. Disclosures: No relevant conflicts of interest to declare.