Boxed Warning on HBV Reactivation for Blood Cancer Drugs

Zosia Chustecka


September 25, 2013

A boxed warning about the risk for reactivation of hepatitis B virus (HBV) infection in patients who once had the virus has been added to the product labeling for 2 drugs used in the treatment of hematological malignancies, rituximab (Rituxan) and ofatumumab (Arzerra), notes the US Food and Drug Administration (FDA).

Both drugs are monoclonal antibodies directed against CD20 and have immunosuppressant effects. In patients who have previously had HBV infection, these effects on the immune system may lead to HBV reactivation.

The FDA notes that some of the cases of HBV reactivation that have been reported with these 2 drugs have resulted in fulminant hepatitis, hepatic failure, and death.

Rituximab is widely used to treat non-Hodgkin's lymphoma and chronic lymphocytic leukemia (CLL), but it is also used in other medical conditions, including rheumatoid arthritis, granulomatosis with polyangiitis, and microscopic polyangiitis.

Ofatumumab was launched in 2009 in the United States for the treatment of CLL in patients who have further disease after treatment with the anticancer drugs fludarabine and alemtuzumab.

Screen All Patients

The problem of hepatitis B reactivation in cancer patients is also seen with chemotherapy, which suppresses the immune system, and there have been calls for HBV screening in all cancer patients who are undergoing chemotherapy, although there has also been some debate over this proposal.

The new labeling for rituximab and ofatumumab now recommends that all patients be screened for HBV before starting treatment with these 2 drugs. Screening should include measurement of both hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc).

If this screening finds evidence of prior HBV infection, physicians treating such patients should consult with hepatitis experts about monitoring of HBV and about the use of HBV antiviral therapy.

Patients with evidence of prior HBV infection should be monitored for clinical and laboratory signs of hepatitis B or HBV reactivation for the whole time that they are undergoing treatment with rituximab and ofatumumab, and also for several months thereafter, since reactivations have occurred several months following completion of therapy with these drugs, the label warns.

The label also states that patients who develop reactivation of HBV while on rituximab or ofatumumab should discontinue the drug immediately, and should be started on appropriate treatment for HBV. In addition, any chemotherapy the patient is receiving should be discontinued until the HBV infection is controlled or resolved.

In patients who develop HBV reactivation hepatitis, no recommendation can be made on whether treatment with rituximab and ofatumumab can be resumed because of a lack of data on this issue, the FDA notes.


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