Daratumumab (Darzalex▼): risk of reactivation of hepatitis B virus

Establish hepatitis B virus status before initiating daratumumab and in patients with unknown hepatitis B virus serology who are already being treated with daratumumab.

Advice for healthcare professionals:

  • hepatitis B virus reactivation has been reported in patients treated with daratumumab, including several fatal cases worldwide
  • screen all patients for hepatitis B virus before initiation of daratumumab; patients with unknown serology who are already on treatment should also be screened
  • monitor patients with positive serology for clinical and laboratory signs of hepatitis B reactivation during treatment, and for at least 6 months following the end of daratumumab treatment
  • advise patients with positive serology to seek medical help immediately if they experience signs and symptoms suggestive of hepatitis B virus reactivation
  • stop treatment with daratumumab in patients with hepatitis B virus reactivation and institute appropriate treatment in consultation with experts in the treatment of hepatitis B virus infection; consult with experts before resuming daratumumab in patients with adequately controlled viral reactivation
  • report any suspected adverse drug reactions associated with daratumumab to the Yellow Card Scheme

Review of cases of hepatitis B reactivation

A recent EU cumulative review of worldwide data has identified reports of hepatitis B virus reactivation in patients treated with daratumumab.

There have been 6 cases of hepatitis B virus reactivation observed in clinical trials in patients with multiple myeloma. Most of these cases were considered non-serious, although fatal hepatitis B virus reactivation cases have been reported in clinical trials. There have also been reports from the post-marketing setting. Nearly all cases have been observed in the first 6 months of daratumumab treatment. In some cases, daratumumab has been reinitiated once hepatitis B virus reactivation has been controlled with antiviral medication.

No cases of hepatitis B virus reactivation associated with daratumumab have been reported in the UK via the Yellow Card Scheme. Nevertheless, prescribers should be vigilant for the risk in UK patients and ensure serology is established in all patients being treated with daratumumab.

Risk factors of hepatitis B reactivation

In patients on daratumumab who have had hepatitis B virus reactivation, risk factors included:

  • previous autologous stem cell transplant (ASCT)

  • concurrent and/or prior lines of immunosuppressive therapy

Residence in or immigration from regions of high hepatitis B prevalence may also present a higher risk of hepatitis B seropositivity.

Identification of the role of daratumumab therapy in the reported cases of hepatitis B virus reactivation is complicated by the underlying medical condition, given that patients with multiple myeloma are immunosuppressed. In several cases, patients were also receiving concomitant medications associated with viral reactivation. However, because a causal relationship cannot be ruled out, the product information for daratumumab will be updated to reflect the new safety information. A letter has been sent to expected prescribers and dispensers of daratumumab.


Daratumumab is indicated:

  • in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant

  • as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a proteasome inhibitor and an immunomodulatory agent and who have demonstrated disease progression on the last therapy

  • in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy

Report any suspected adverse drug reactions

Daratumumab▼ is subject to additional monitoring and any suspected adverse drug reactions (ADR) should be reported to the Yellow Card Scheme. Report on the Yellow Card website or via the Yellow Card app (download via iTunes Yellow Card for iOS devices or via PlayStore Yellow Card for Android devices).

Reporting suspected ADRs, even those known to occur, adds to knowledge about the frequency and severity of these reactions and can be used to identify patients who are most at risk. Your report helps the safer use of medicines.

Article citation: Drug Safety Update volume 13, issue 1: August 2019: 1.

Published 19 August 2019