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Rituximab, chemotherapy led to HBV reactivation in lymphoma patients

Rituximab and CHOP-based chemotherapy led to hepatitis B virus reactivation among some patients with lymphoma, according to new study data.

Researchers in Taiwan conducted a prospective study of 150 patients with lymphoma and resolved hepatitis B virus (HBV) infection from 11 medical centers. Patients received first-line rituximab-cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP)-based chemotherapy (median treatment, six cycles per patient). HBV DNA was recorded at baseline and every 4 weeks for 1 year after completing chemotherapy. Patients who endured HBV reactivation — defined as a greater than 10-fold increase in HBV DNA — were treated with 0.5 mg entecavir daily for 48 weeks. Median follow-up, as of April 1, 2013, was 27.4 months.

HBV reactivation occurred in 17 patients; nine episodes occurred during rituximab-CHOP chemotherapy for an incidence rate of 10.4 per 100 person-years. HBV-related hepatitis flares — defined as a threefold increase in serum ALT level beyond 100 IU/L — occurred in 6.4 cases of every 100 person-years. Hepatitis B surface antigen became positive in 12 patients, and hepatitis B e antigen was evident in seven patients. There were 59 complete responses and 47 partial responses to chemotherapy among 138 patients who had measurable tumors at baseline (76.8%; 95% CI, 68.9-83.6).

Three-year progression-free survival (PFS) and overall survival (OS) rates were 67.3% and 72.9%, respectively. Univariate analysis revealed that patients who experienced HBV reactivation had a lower OS rate (HR=1.93; 95% CI, 0.85-4.4) and lower PFS rate (HR=1.72; 95% CI, 0.64-4.8). In multivariate analysis, response to rituximab-CHOP chemotherapy was the only independent predictor for PFS (HR=0.09; 95% CI, 0.04-0.18). More than 10% of patients experienced a serious adverse event, including infection (n=32) and febrile neutropenia (n=27).

“The results … indicate that in lymphoma patients with resolved HBV infection, HBV reactivation induced by rituximab-CHOP chemotherapy is not uncommon and clinically significant,” the researchers concluded. “The evidence calls for a universal screening for HBV serological markers for lymphoma patients before starting chemotherapy.”

Disclosure: Ann-Lii Cheng, MD, reports she consults for Eisai and advises Daiichi Sankyo.