SUMMARY  

• Hepatitis B virus (HBV) reactivation, in some cases fatal, has been reported in patients treated with DARZALEX for intravenous (IV) use and DARZALEX FASPRO for subcutaneous (SC) use. HBV screening should be performed in all patients before initiation of treatment with DARZALEX or DARZALEX FASPRO.^{1, 2}
• For patients with evidence of positive HBV serology, monitor for clinical and laboratory signs of HBV reactivation during, and for at least six months following the end of DARZALEX or DARZALEX FASPRO. Manage patients according to current clinical guidelines. Consider consulting a hepatitis disease expert as clinically indicated.^{1, 2}
• In patients who develop reactivation of HBV while on DARZALEX or DARZALEX FASPRO, suspend treatment and any concomitant steroids, chemotherapy, and institute appropriate treatment. Resumption of DARZALEX or DARZALEX FASPRO treatment in patients whose HBV reactivation is adequately controlled should be discussed with physicians with expertise in managing HBV.^{1, 2}

PRODUCT LABELING

• DARZALEX (daratumumab) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX-pi.pdf. 
• DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX+Faspro-pi.pdf.

BACKGROUND

Reactivation of HBV is a syndrome marked by the abrupt reappearance or rise of HBV deoxyribonucleic acid (DNA) in the serum of a patient with previously inactive or resolved HBV infection. Reactivation may be accompanied by reappearance of disease activity or a flare of hepatitis in previously minimal or inactive disease. The consequences of HBV reactivation range from a self-limited hepatitis to fulminant hepatic failure and death. HBV reactivation can occur spontaneously, but more typically is triggered by immunosuppressive therapy of cancer, autoimmune disease, or organ transplantation.^{3, 4}

There are no clear-cut diagnostic criteria for HBV reactivation. It is characterized by 2 main parameters: rising serum HBV DNA followed by rising alanine aminotransferase (ALT). Rising HBV DNA levels usually precede ALT elevation, which frequently lags by several days (range, 1 to 11 weeks) after an increase in viral load. Furthermore, HBV DNA levels may be declining or undetectable by the time a rise in ALT is noticed.⁵

In patients undergoing chemotherapy for the treatment of malignant disease, the reactivation of HBV in hepatitis B surface antigen (HBs Ag) positive patients has been frequently reported. Reactivation has also been reported in HBs Ag negative patients who test positive for hepatitis B core antibody (HBc Ab) and/or hepatitis B surface antibody (HBs Ab).⁶ The impaired immunity associated with the underlying malignancy or the chemotherapy induced immunosuppression predisposes these patients to the development of new infections or reactivations of common viruses. Rates of HBV reactivation in HBV carriers who undergo chemotherapy range from 14% to 72%. Possible explanations for this wide variation include differences in patient populations, types of tumors, chemotherapy regimens, definitions of reactivation, and study designs.⁷

Reactivation more frequently follows cessation of chemotherapy but may occur during chemotherapy. The reported interval ranges from 4 to 36 weeks (median, 16 weeks) from initiation of chemotherapy.^{5, 8}

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 27 March 2024.