Abstract
Background:
Due to the high rate of chronic hepatitis B virus (HBV) infection in China, hepatitis B surface antigen (HBsAg) can be detected among 25-61% of patients with diffuse large B-cell lymphoma (DLBCL) and 20-40% with follicular lymphoma (FL), while HBsAg- negative (neg) /HBcAb-positive (pos) can be detected among 20-44% of patients with DLBCL (Chinese Society of Hematology, 2013). When these patients receive immune-suppressing treatment, they are at an increased risk of HBV reactivation which may lead to hepatic mortality and interrupt the rituximab-based chemotherapy. For patients and their physicians, HBV infection management plays a crucial role for achieving optimal survival outcomes without compromising safety. This multicenter, single-arm, prospective, non-interventional study was conducted at 24 centers in China between January 17, 2011 and October 31, 2016. Previously untreated CD20-positive DLBCL patients who were eligible to receive rituximab plus chemotherapy (R-chemo) (CHOP or non-CHOP) as first-line treatment were enrolled with no specific exclusion criteria. We investigated the risk of HBV reactivation in patients with CD20+ DLBCL or FL which received R-chemo as first-line treatment.
Methods:
Patients who received at least one dose of R-chemo were included in the analysis. Data were collected and analyzed from medical records for 3 years since the last R dose was administered. The evaluation of HBV infection management included HBV infection and liver function screening before R-chemo, viral replication monitoring during and after R-chemo, antiviral prophylaxis use and HBV reactivation rates. HBsAg-pos patients had HBV reactivation if HBV DNA increased ≥1 log10 from baseline, if HBV DNA appeared (above the lower limit of detection) or if HBeAg appeared in HBeAg- neg patients. HBsAg-neg/HBcAb-pos patients had HBV reactivation if there was appearance of either HBsAg or HBV DNA (above the lower limit of detection). The HBV reactivation was determined by SAP and investigator's judgment. This study was registered in clincialtrials.gov (NCT01340443).
Results:
In total, 282 DLBCL patients and 31FL patients were included in the analysis. HBV screening data were available from 271 enrolled patients. At baseline, 26 patients were HBsAg-pos, 79 were HBsAg- neg/HBcAb-pos and 166 were double neg. HBV infection status was undefined for 42 patients. During the study, HBV reactivation was detected in 8 patients, which was only in the DLBCL group. Seven cases were observed in treatment period, while 1 case occurred during 3-year follow-up. None of them led to study termination, temporary termination, or dose adjustment.
Cox univariate regression analysis in DLBCL patients showed that baseline type of hepatitis B correlated with overall response rate (ORR) and complete response (CR) but had no effect on progression-free survival (PFS).
In term of HBV infection management, in DLBCL group, 25 patients with HBsAg-pos or HBsAg-neg/ HBcAb-pos receiving antiviral prophylaxis. In FL group, only 3 patients received antiviral treatment. Lamivudine was mostly administered by Chinese investigators. Details on treatment, duration and infection status are listed in Table 1.
Summary:
In this prospective, observational study, we followed the patients with DLBCL or FL for 3 years to investigate the risk of HBV reactivation after they received R-chemo. Our study showed that, in real-world setting, the incidence of HBV reactivation in patients with a history of hepatitis, particularly those positive for HBsAg is acceptable, baseline type of hepatitis B had no effect on PFS. Close monitoring and antiviral prophylaxis would be beneficial to the patients with DLBCL or FL combined with hepatitis B infection while they receive R-chemo.
No relevant conflicts of interest to declare.
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