Risk of hepatitis B virus reactivation with pomalidomide

Pomalidomide (Pomalyst®, Celgene Pte Ltd) is an immunomodulating agent that is structurally related to thalidomide. It has been licensed locally since December 2014 for used in combination with dexamethasone for the treatment of adult patients with relapsed and refractory multiple myeloma (MM), who have received at least two prior treatment regimens (including lenalidomide and bortezomib) and have demonstrated disease progression on the last therapy. As a structural analogue of thalidomide, a known human teratogen, a teratogenic effect cannot be ruled out when Pomalyst® is taken during pregnancy. In order to minimise the risk of teratogenicity associated with its use, Pomalyst® is currently available locally under the Pregnancy Prevention Programme (i-access® programme) where healthcare professionals who wish to prescribe or dispense Pomalyst® to their patients will need to be enrolled. 

Overseas cases of HBV reactivation with pomalidomide

Cases of HBV reactivation have been reported rarely (incidence less than 0.1%) following treatment with pomalidomide in combination with dexamethasone. In some of these cases, HBV reactivation was reported to have progressed to hepatic failure.1

The cases of HBV reactivation generally occurred during early phase of treatment with pomalidomide, with most reports received within the first treatment cycle. Patients treated with pomalidomide usually have existing risk factors for viral reactivation including old age, underlying progressive MM and prior treatment with multiple immunosuppressive treatments. The immunosuppressive effect of pomalidomide, in combination with dexamethasone, may further increase the risk of viral reactivation in these patients.

Review by the European Medicines Agency (EMA)

In March 2016, the EMA's Pharmacovigilance Risk Assessment Committee (PRAC) completed a safety review on the association of HBV reactivation with pomalidomide use. The review assessed clinical studies and cases of suspected adverse drug reactions reported by healthcare professionals and in literature.2

As of 7 August 2015, five patients were identified to have developed HBV reactivation while receiving treatment with pomalidomide. Two cases resulted in acute hepatic failure, one of which had a fatal outcome. Four cases occurred within a month of initiating pomalidomide therapy. Two of the cases of HBV reactivation reviewed by PRAC were reported from the literature.3,4 The first case was a 56-year old man diagnosed with IgG kappa MM who had received multiple chemotherapies after stem cell transplants and was started on monotherapy with pomalidomide when he experienced jaundice with abnormal liver function tests. His laboratory test results showed positive HbsAg, hepatitis B envelope antigen (HbeAg) and HBV DNA >8.2 log10 IU/ml. He was previously tested to be anti-HBc positive and HBsAg negative. The second case was a 68-year old woman with refractory MM who received pomalidomide and dexamethasone together with multiple drugs including anthracyclines, alkylators and proteasome inhibitors. She initially suffered from major hematological toxicities and infectious complications including HBV reactivation, but later experienced long-term disease control upon careful dose adjustments and selection of combination drugs.

Based on the assessment results, recommendations were made by PRAC to update the product information of pomalidomide with warnings on infections and HBV reactivation, as well as to distribute a safety communication to healthcare professionals to inform on the need to establish the HBV status of patients before initiating treatment with pomalidomide.5

Local situation and HSA’s advisory

To date, HSA has not received any local reports of HBV reactivation with pomalidomide use.

The Singapore package insert of Pomalyst® currently warns of the risk of hepatitis and HSA is working with the company to strengthen the warnings on the risk of HBV reactivation.

Healthcare professionals are encouraged to exercise caution when prescribing pomalidomide in patients previously infected with HBV and to establish the HBV status of their patients before initiating treatment with pomalidomide.

References:

  1. https://assets.publishing.service.gov.uk/media/
    5731b28be5274a037b000003/DHPC_Imnovid_final_proof_UK.pdf
  2. Drug Safety Update 2016 May; 9:10
  3. Ann Hepatol 2014; 13: 461-65
  4. Case Rep Oncol 2015; 8: 189-95
  5. http://www.ema.europa.eu/docs/en_GB/document_library/Minutes/
    2016/05/WC500205893.pdf
Healthcare professional, Industry member, Therapeutic Products
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