EMA Reviews Risks Associated with Painkillers and CAR T-Cell Medicines

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The European Medicines Agency (EMA) announced on June 14, 2024 that the agency’s Pharmacovigilance Risk Assessment Committee (PRAC) is evaluating potential risks associated with the painkiller metamizole. PRAC is also researching the possible risk of secondary cancers developing in patients who are treated with chimeric antigen receptor (CAR) T-cell medicines.

According to EMA, concerns that measures put in place to minimize the risk of agranulocytosis in the painkiller metamizole might not be adequate. Drugs containing metamizole are authorized in the European Union, varying from country to country, for treating moderate to severe pain and fever. These medicines have a known side effect, agranulocytosis, where a sudden drop in white blood cells occurs. Agranulocytosis is a rare or very rare side effect that may lead to serious, and possibly fatal, infections. There are measures set by EU countries to minimize the risk; however, PRAC is looking into the effectiveness of these measures.

Regarding CAR T-cell medicines, PRAC states that patients receiving these treatments should be monitored for the rest of their lives for secondary cancers. New cancers, different from the original malignancy, may develop after treatment with CAR T-cell medicines.

PRAC came to this conclusion after reviewing data from 38 cases of secondary malignancies of T-cell origin in approximately 42,500 patients. “Tissue samples were tested in half of the cases, revealing the presence of the CAR construct in 7 cases. This suggests that the CAR T-cell medicine was involved in disease development. The secondary malignancies of T-cell origin have been reported within weeks and up to several years following administration of CAR T-cell medicines. Patients treated with these medicines should be monitored life-long for new malignancies,” EMA stated in a press release (1).

Product information, which has advisory information about secondary malignancies, will be updated to include new information about T-cells. PRAC is discussing direct healthcare professional communication about CAR T-cell medicines and will inform professionals about its new conclusion.

There are six approved CAR T-cell treatments in the EU: Abecma, Breyanzi, Carvykti, Kymriah, Tecartus, and Yescarta. They treat a range of blood cancers.

In November 2023, FDA in the United States announced it was investigating the risk of T-cell malignancy following CAR T-cell immunotherapies (2). “Although the overall benefits of these products continue to outweigh their potential risks for their approved uses, FDA is investigating the identified risk of T cell malignancy with serious outcomes, including hospitalization and death, and is evaluating the need for regulatory action,” FDA states on its website. “The initial approvals of these products included postmarketing requirements (PMRs) under Section 505(o) of the Federal Food, Drug, and Cosmetic Act (FDCA) to conduct 15-year long term follow-up observational safety studies to assess the long-term safety and the risk of secondary malignancies occurring after treatment.” The agency also said that patients of these treatments should be monitored for life for new malignancies.

References

1. EMA. Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 10-13 June 2024. Press Release. June 14, 2024.
2. FDA. FDA Investigating Serious Risk of T-cell Malignancy Following BCMA-Directed or CD19-Directed Autologous Chimeric Antigen Receptor (CAR) T Cell Immunotherapies. Nov. 28, 2024. https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/fda-investigating-serious-risk-t-cell-malignancy-following-bcma-directed-or-cd19-directed-autologous