Carfilzomib (Kyprolis▼): risk of reactivation of hepatitis B virus

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

From:
Medicines and Healthcare products Regulatory Agency
Published
21 November 2019
Therapeutic area:
Cancer, GI, hepatology and pancreatic disorders, Haematology, Infectious disease

Advice for healthcare professionals:

  • hepatitis B virus reactivation has been reported in patients treated with carfilzomib

  • screen all patients for hepatitis B virus before initiation of carfilzomib; patients with unknown serology who are already on treatment should also be screened

  • consider prophylaxis with antivirals for patients with positive serology who are treated with carfilzomib

  • monitor patients with positive serology for clinical and laboratory signs of hepatitis B reactivation during and after treatment

  • advise patients with positive serology to seek medical help immediately if they experience signs and symptoms suggestive of hepatitis B virus reactivation

  • in patients who have hepatitis B reactivation, it is recommended to consult relevant experts when making decisions regarding hepatitis B virus treatment and the continuation, interruption, or resumption of carfilzomib

  • report any suspected adverse drug reactions associated with carfilzomib to the Yellow Card Scheme

Review of cases of hepatitis B reactivation

Carfilzomib (Kyprolis▼) is indicated in combination with lenalidomide and dexamethasone or with only dexamethasone for the treatment of adult patients with multiple myeloma who have received at least 1 prior therapy.

A recent EU review of clinical studies and cases of suspected adverse drug reactions has identified reports of hepatitis B reactivation associated with carfilzomib. Following the review, changes are being made to the Summary of Product Characteristics to recommend screening for hepatitis B virus before a patient starts carfilzomib treatment. Screening is also recommended for patients already under treatment with carfilzomib with unknown hepatitis B virus serology.

Details of cases reported

The review assessed cases worldwide up to 10 July 2019 and identified a total of 23 cases from clinical studies and post-marketing.

In clinical studies, 8 serious cases of hepatitis B virus reactivation were identified. Of these, 5 cases had a plausible temporal association and liver function abnormalities and reported an improvement in the patient’s clinical condition once the medicine was stopped (positive dechallenge).

The review also identified 15 cases of hepatitis B virus reactivation in the post-marketing period. Most of these cases (93%; 14 cases) were serious. Reactivation was reported in 12 men and 3 women, with a median patient age of 70 years (range 41 to 78 years). The worldwide cumulative post-marketing exposure for carfilzomib is approximately 108 900 patients (42 200 patient-years) up to 19 January 2019.[footnote 1]

Of the 13 post-marketing cases in which baseline serology was reported: 3 cases were positive for hepatitis B core antibodies (anti-HBc), 5 cases were negative for hepatitis B surface antigen (HBsAg), 1 case had negative anti-HBc, and 4 had undetected hepatitis B DNA. After diagnosis of hepatitis B virus reactivation, positive HBsAg was reported in 3 cases, with hepatitis B DNA elevated in 4 cases.

Most cases (80%;12) had a plausible temporal association. In 5 cases, the reports indicated the patients’ clinical condition improved once the medicine was stopped, and in 1 case, worsened again once the medicine was restarted. 11 patients received treatment with an anti-hepatitis B medicine. In 5 cases, carfilzomib treatment was continued, and the patient recovered from the hepatitis infection.

Report any suspected adverse drug reactions

Carfilzomib 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 4: November 2019: 2.

  1. Provided to the MHRA by Amgen. October 2019. Exposure is cumulative from 20 July 2012 (the date the product was first authorised world-wide). ↩

Updates to this page

Published 21 November 2019
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