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
• Tak et al (2026)³ reported the results of a retrospective study evaluating the incidence and risk of HBV reactivation in patients treated with anti-cluster of differentiation (CD) 38 therapy who were hepatitis B core antibody (HBc Ab) positive and hepatitis B surface antigen (HBs Ag)-negative. Patients with both low hepatitis B surface antibody (HBs Ab) titers and treated later line with anti-CD38 therapy were classified as high-risk. Of the patients that did not receive nucleotide/nucleoside analogue (NA) prophylaxis, 7.8% experienced HBV reactivation; no patients in the NA prophylaxis group experienced HBV reactivation. After 24 months, 3.9% of patients experienced severe hepatitis and 1.7% experience liver-related death.

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.^{4, 5}

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.⁶

In patients undergoing chemotherapy for the treatment of malignant disease, the reactivation of HBV in HBs Ag positive patients has been frequently reported. Reactivation has also been reported in HBs Ag negative patients who test positive for HBc Ab and/or HBs Ab.⁷ 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.⁸

Reactivation most 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.^6,9

ClINICal data

Tak et al (2026)³ reported the results of a retrospective study evaluating the incidence and risk of HBV reactivation in patients treated with anti-CD 38 therapy who were HBc Ab positive and HBs Ag negative.

Study Design/Methods

• Inclusion criteria: multiple myeloma, treated with DARZALEX or DARZALEX FASPRO, HBc Ab positive, HBs Ag negative.³
• Based on HBs Ab titers (<100 IU/L vs ≥100 IU/L) and DARZALEX or DARZALEX FASPRO line of therapy (first-line vs later-line), patients were stratified into risk groups.³
• Virological markers and liver function tests were monitored every 1-3 months.³
• Primary endpoint: HBV reactivation.¹⁰
• Secondary endpoints: severe hepatitis, liver-related mortality.¹⁰

Results

Patient Characteristics

• Between January 2015 and December 2025, a total of 180 patients were assessed.³
• Fourteen patients (7.8%) received prophylactic NA treatment. Baseline characteristics by NA therapy are summarized in Table: Baseline Characteristics.¹⁰ 

Safety

• All HBV reactivation events occurred only in the NA untreated group (7.8% [n=13]).³
• At a median follow-up of 10.6 months, the crude incidence of HBV reactivation in the high-risk subgroup was 19.6% (n=11).^3,10 
  • At 24 months, the cumulative incidence of HBV reactivation in the high-risk group was nearly 40%.³
• Patients in the low-risk group did not experience any HBV reactivation events.³
• Liver-related clinical outcomes are summarized in Table: Liver-Related Outcomes.^3,10

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 11 March 2026.