Entecavir vs lamivudine for prevention of hepatitis B virus reactivation among patients with untreated diffuse large B-cell lymphoma receiving R-CHOP chemotherapy: a randomized clinical trial.

He Huang, Xueying Li, Jun Zhu, Sheng Ye, Hongyu Zhang, Wei Wang, Xiangyuan Wu, Jiewen Peng, Bing Xu, Yingcheng Lin, Yabing Cao, Haoran Li, Suxia Lin, Qing Liu, Tongyu Lin

Index: JAMA 312(23) , 2521-30, (2014)

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Abstract

Hepatitis B virus (HBV) reactivation is a serious complication for patients with lymphoma treated with rituximab-containing chemotherapies, despite lamivudine prophylaxis treatment. An optimal prophylactic antiviral protocol has not been determined.To compare the efficacy of entecavir and lamivudine in preventing HBV reactivation in patients seropositive for the hepatitis B surface antigen with untreated diffuse large B-cell lymphoma receiving chemotherapy treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).Randomized, open-label, phase 3 study conducted from February 2008 through December 2012 at 10 medical centers in China. This study was a substudy of a parent study designed to compare a 3-week with a 2-week R-CHOP chemotherapy regimen for untreated diffuse large B-cell lymphoma. Patients enrolled in the parent study who were seropositive for the hepatitis B surface antigen and had normal liver function, serum HBV DNA levels of less than 103 copies/mL, and no prior antiviral therapy were randomized to entecavir (n = 61) or lamivudine (n = 60).Daily entecavir (0.5 mg) or lamivudine (100 mg) beginning 1 week before the initiation of R-CHOP treatment to 6 months after completion of chemotherapy.The primary efficacy end point was the incidence of HBV-related hepatitis. The secondary end points included rates of HBV reactivation, chemotherapy disruption due to hepatitis, and treatment-related adverse events.There were 121 patients randomly assigned to receive entecavir (n = 61) or lamivudine (n = 60). The date of last patient follow-up was May 25, 2013. The rates were significantly lower for the entecavir group vs the lamivudine group for HBV-related hepatitis (0% vs 13.3%, respectively; difference between groups, 13.3% [95% CI, 4.7% to 21.9%]; P = .003), HBV reactivation (6.6% vs 30%; difference, 23.4% [95% CI, 10.2% to 36.6%]; P = .001), and chemotherapy disruption (1.6% vs 18.3%; difference, 16.7% [95% CI, 6.4% to 27.0%]; P = .002). Of the 61 patients in the entecavir group, 15 (24.6%) experienced treatment-related adverse events. Of 60 patients in the lamivudine group, 18 (30%) experienced treatment-related adverse events (difference between entecavir and lamivudine groups, 5.4% [95% CI, -10.5% to 21.3%]; P = .50).Among patients seropositive for the hepatitis B surface antigen with diffuse large B-cell lymphoma undergoing R-CHOP chemotherapy, the addition of entecavir compared with lamivudine resulted in a lower incidence of HBV-related hepatitis and HBV reactivation. If replicated, these findings support the use of entecavir in these patients.clinicaltrials.gov Identifier: NCT01793844; Chinese Clinical Trial Registry Identifier: CTR-TRC-11001687.