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JAMA. 2014 Dec 17;312(23):2521-30. doi: 10.1001/jama.2014.15704.

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.

Author information

1
Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
2
Department of Medical Oncology, Beijing Cancer Hospital, Beijing, China.
3
Department of Medical Oncology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
4
Department of Medical Oncology, Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China.
5
Cancer Center of the First People's Hospital of Foshan, Foshan, China.
6
Department of Medical Oncology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
7
Cancer Center of People's Hospital of Zhongshan, Zhongshan, China.
8
Department of Hematology, Southern Hospital of Southern Medical University, Guangzhou, China.
9
Department of Medical Oncology, Cancer Hospital, Shantou University Medical College, Shantou, China.
10
Cancer Center of Kiang Wu Hospital, Macau, China.
11
Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China.
12
Department of Epidemiology and Biostatistics, Sun Yat-sen University Cancer Center, Guangzhou, China.

Abstract

IMPORTANCE:

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.

OBJECTIVE:

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).

DESIGN, SETTING, AND PATIENTS:

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).

INTERVENTIONS:

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.

MAIN OUTCOMES AND MEASURES:

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.

RESULTS:

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).

CONCLUSIONS AND RELEVANCE:

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.

TRIAL REGISTRATIONS:

clinicaltrials.gov Identifier: NCT01793844; Chinese Clinical Trial Registry Identifier: CTR-TRC-11001687.

PMID:
25514302
DOI:
10.1001/jama.2014.15704
[Indexed for MEDLINE]

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