Randomized prospective study evaluating tenofovir disoproxil fumarate prophylaxis against hepatitis B virus reactivation in anti-HBc-positive patients with rituximab-based regimens to treat hematologic malignancies: The Preblin study

Abstract

BackgroundHepatitis B virus (HBV) reactivation in patients with resolved HBV infection (HBsAg negative, antiHBc positive) is uncommon, but potentially fatal. The role of HBV prophylaxis in this setting is uncertain. The aim of this study was to compare the efficacy of tenofovir disoproxil fumarate (TDF) prophylaxis versus close monitoring in antiHBc-positive, HBsAg-negative patients under treatment with rituximab (RTX)-based regimens for hematologic malignancy.MethodsPREBLIN is a phase IV, randomized, prospective, open-label, multicenter, parallel-group trial conducted in 17 hospitals throughout Spain. Anti-HBc-positive, HBsAg-negative patients with undetectable HBV DNA were randomized to receive TDF 300 mg once daily (Group I) or observation (Group II). The primary endpoint was the percentage of patients showing HBV reactivation during 18 months following initiation of RTX treatment. Patients with detectable HBV DNA (Group III) received the same dose of TDF and were analyzed together with Group I to investigate TDF safety.ResultsSixty-one patients were enrolled in the study, 33 in the TDF treatment group and 28 in the observation group. By ITT analysis, HBV reactivation was 0% (0/33) in the study group and 10.7% (3/28) in the observation group (p = 0.091). None of the patients in either group showed significant differences in liver function parameters between baseline and the last follow-up sample. TDF was generally well tolerated and there were no severe treatment-related adverse events.ConclusionIn patients with hematological malignancy and resolved hepatitis B infection receiving RTX-based regimens, HBV reactivation did not occur in patients given TDF prophylaxis.

Prevention of hepatitis B virus reactivation in patients with hematological malignancies and resolved hepatitis B virus infection: a systematic review and meta‐analysis

“…Altogether 386 citations were screened after the initial literature search and 13 studies including 1748 patients that were published between 2009 and 2019 were ultimately included after detailed assessment and review. The studies in the final meta-analysis comprised three prospective studies [20][21][22] and ten retrospective studies. 15,[23][24][25][26][27][28][29][30][31] Table 1 summarizes the characteristics of the included studies.…”

“…In contrast, in the pooled analysis of the 10 retrospective studies (n = 1257), the estimated RR was 0.89 (95% CI 0.31-2.52, P = 0.82). Six of the included studies21,[23][24][25]29,30 reported zero HBV reactivation events in the antiviral prophylaxis group.…”

Hepatitis B management during immunosuppression for haematological and solid organ malignancies: an Australian consensus statement

“…In this group, the optimal duration of prophylaxis is controversial and international guidelines differ in their recommendations. Double‐blinded randomised controlled trials of entecavir and tenofovir prophylaxis in HBsAg negative and anti‐HBc positive patients taking rituximab show that 12 months of therapy significantly reduces the risk of HBV reactivation and that HBV reactivation may occur up to 12 months after immunosuppression cessation . Based on these data, overseas guidelines recommend at least 12–18 months of therapy after using B cell‐depleting, B cell active or anti‐CD20 agents, including during and after maintenance therapy, to ensure all cases of reactivation are captured .…”

Hepatitis B: Who and when to treat?

“…Viraemic patients should be treated in the same way as HBsAg‐positive patients . Antiviral prophylaxis is recommended in the high‐risk group (>10%), including anti‐HBc‐positive subjects who require rituximab or those undergoing stem cell transplantation . Prophylaxis should continue for at least 18 months after stopping immunosuppression, and patients should be monitored for at least 12 months after prophylaxis is discontinued .…”

“…4,34,36 Antiviral prophylaxis is recommended in the high-risk group (>10%), including anti-HBc-positive subjects who require rituximab or those undergoing stem cell transplantation. 38 Prophylaxis should continue for at least 18 months after stopping immunosuppression, and patients should be monitored for at least 12 months after prophylaxis is discontinued. 4 In HBsAg-negative, anti-HBc-positive subjects with a moderate (<10%) or low (<1%) risk of HBV reactivation, preemptive therapy rather than prophylaxis, is generally recommended.…”