Bortezomib-Induced Hepatitis B Reactivation

Abstract

Background. It has recently been reported that hepatitis B (HBV) reactivation often occurs after the use of rituximab and stem cell transplantation in patients with lymphoma who are hepatitis B surface antigen (HBsAg) negative. However, clinical data on HBV reactivation in multiple myeloma (MM) is limited to only a few reported cases. Bortezomib and lenalidomide have remarkable activity in MM with manageable toxicity profiles, but reactivation of viral infections may emerge as a problem. We present a case of MM that developed HBV reactivation after bortezomib and lenalidomide therapy. Case Report. A 73-year-old female with a history of marginal cell lymphoma was monitored without requiring therapy. In 2009, she developed MM, presenting as a plasmacytoma requiring vertebral decompression and focal radiation. While receiving radiation she developed renal failure and was started on bortezomib and liposomal doxorubicin. After a transient response to 5 cycles, treatment was switched to lenalidomide. Preceding therapy initiation, her serology indicated resolved infection. Serial monitoring for HBV displayed seroconversion one month after change in therapy. Conclusion. Bortezomib associated late HBV reactivation appears to be a unique event that requires further confirmation and brings to discussion whether hepatitis B core positive individuals would benefit from monitoring of HBV activation while on therapy.

Hepatitis B infection reported with cancer chemotherapy: analyzing the US FDA Adverse Event Reporting System

“…Bortezomib and thalidomide are used in treating MM. Several cases of hepatitis B infection associated with BOR have been reported . CPA, DXR, and melphalan (L‐PAM) are also used in the treatment of MM, and lenalidomide may be indicated for MM.…”

Association between hepatitis B virus infection and risk of multiple myeloma: a systematic review and meta‐analysis

“…All patients with HBV infection who subsequently develop MM are at risk for reactivation following chemotherapy, particularly following immunosuppressive chemotherapy. Several recent studies found a significantly higher occurrence of HBV reactivation and/or hepatic damage after patients with HBV infection underwent chemotherapy, especially protocols containing high doses of glucocorticoids or proteasome inhibitor bortezomib, which are the commonly used agents in the treatment of MM. The mechanism of HBV reactivation in association with chemotherapy is unclear.…”

“…HBV DNA contains a glucocorticoid‐responsive element that reportedly facilitates HBV replication . Bortezomib may alter the number and function of CD8 T cells and CD56 natural killer cells, and HBV reactivation may be attributable to the effect of bortezomib on cell‐mediated immunity . In addition, patients with concurrent MM and HBV infection reportedly experience more and earlier hepatic adverse events while undergoing chemotherapy .…”

Hepatitis B reactivation in multiple myeloma patients with resolved hepatitis B undergoing chemotherapy

“…Therefore, bortezomib, mainly by inhibition of the NF‐κB pathway, may increase the risk of viral infections. Clinical data on HBV reactivation in patients receiving bortezomib in MM are limited to only a few reported cases . Li et al .…”