Summary Safety Review - Breyanzi (lisocabtagene maraleucel), Carvykti (ciltacabtagene autoleucel), Kymriah (tisagenlecleucel), Tecartus (brexucabtagene autoleucel) and Yescarta (axicabtagene ciloleucel) - Chimeric Antigen Receptor T-cell (CAR-T) Therapies - Assessing the Potential Risk of Secondary T-cell Malignancy

Breyanzi (lisocabtagene maraleucel), Carvykti (ciltacabtagene autoleucel), Kymriah (tisagenlecleucel), Tecartus (brexucabtagene autoleucel) and Yescarta (axicabtagene ciloleucel) - Chimeric antigen receptor T-cell (CAR-T) therapies

Secondary T-cell malignancy (a new cancer, that forms in a type of white blood cells called T-cells, after starting CAR-T therapy to treat other forms of blood cancers)

• Health Canada’s safety review found a possible link between CAR-T therapies and the risk of secondary T-cell malignancy.

• Health Canada is working with the manufacturers to align the product safety information in the Canadian product monograph (CPM) for all CAR-T therapies to include information about the risk of secondary T-cell malignancy.

• Manufacturers will also be required to update their product’s educational materials to include information about this risk and a recommendation for life-long monitoring of patients for secondary T-cell malignancies.

• Health Canada will inform healthcare professionals about these updates through a Health Product InfoWatch communication.

Health Canada reviewed the potential risk of secondary T-cell malignancy associated with the use of CAR-T therapies. The safety review was triggered by a labelling update in the United States for all CAR-T therapies. 

In 2024, the manufacturers of some CAR-T therapies (Yescarta, Tecartus, Carvykti and Kymriah) updated the CPM for those products to include the risk of secondary T-cell malignancy.

• Chimeric antigen receptor T-cell therapies are a type of gene therapy authorized for sale in Canada for the treatment of various blood cancers, including certain types of leukemia (cancer in the blood and bone marrow), lymphoma (cancer that forms in the immune cells of the lymphatic system) and multiple myeloma (cancer that forms in a type of white blood cell called a plasma cell) in patients whose cancer has relapsed (come back) or is refractory (has stopped responding to previous treatment). These treatments use a patient’s own T-cell to find and attack cancer cells throughout their body.

• Chimeric antigen receptor T-cell therapies have been available in Canada since 2019. Five CAR-T therapies are authorized in Canada: Breyanzi, Carvykti, Kymriah, Tecartus and Yescarta.

• Between 2019 and 2024, 669 patients have been treated with CAR-T therapies in Canada.

• Health Canada reviewed the available information provided by manufacturers and foreign regulatory agencies, as well as from searches of the Canada Vigilance database^a and the scientific literature.

• Health Canada reviewed 30 cases (1 Canadian and 29 international) of secondary T-cell malignancy in patients undergoing CAR-T therapies. Of those 30 cases, 6 were found to be probably linked to the CAR-T therapies, 9 were found to be possibly linked, 9 were found unlikely to be linked and 6 (1 Canadian) could not be assessed due to missing information.

• Of the probable or possible cases, the diagnosis of secondary T-cell malignancy ranged from 29 days to over 3 years following administration of CAR-T therapy

• Ten deaths were reported among the 30 cases reviewed by Health Canada, with 5 occurring in cases found to be probably or possibly linked to the CAR-T therapies. However, it was not possible to determine whether the deaths were related to the CAR-T therapies due to insufficient information about the cause of death.

• Patients who receive CAR-T therapies generally have advanced B-cell lymphoma or multiple myeloma and have failed other cancer therapies, including chemotherapy. Both the underlying diseases and prior therapies are important risk factors in developing T-cell malignancy. However, the role of the CAR-T therapy in the development of a secondary cancer could not be excluded.

• Health Canada’s review of the available information concluded that there is a possible link between CAR-T therapies and the risk of secondary T-cell malignancy.

• Health Canada is working with the manufacturers to align the CPM for all CAR-T therapies to include information about the risk of secondary T-cell malignancy.

• Manufacturers will be required to update their product’s educational materials to include information about this risk and a recommendation for life-long monitoring of patients for secondary T-cell malignancies. They will also be required to update testing procedures for patients with secondary T-cell malignancies, monitor data for this risk in Canada and other jurisdictions, and provide updates to Health Canada for the next 3 years.

• Health Canada will inform healthcare professionals about these updates through a Health Product InfoWatch communication.

• Health Canada encourages consumers and healthcare professionals to report any side effects related to CAR-T therapies, and other health products, to the  Canada Vigilance Program.

• Health Canada will continue to monitor safety information involving CAR-T therapies, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should new health risks be identified. 

The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information, and what is known about the use of CAR-T therapies both in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.

1. Canadian reports can be accessed through the Canada Vigilance Online Database.