Summary Safety Review - Keytruda (pembrolizumab) and Tecentriq (atezolizumab) - Assessing the Potential Risk of Aplastic Anemia

Keytruda (pembrolizumab) and Tecentriq (atezolizumab)

Aplastic anemia, a condition in which the body stops producing enough new blood cells

• Keytruda (pembrolizumab) and Tecentriq (atezolizumab) are anti-cancer agents belonging to a class of drugs called immune checkpoint inhibitors (ICIs). They are authorized for sale in Canada to treat different types of cancers.

• Health Canada reviewed the potential risk of aplastic anemia with the use of Keytruda or Tecentriq. The safety review was triggered by safety information received from the manufacturers and published in the medical literature.

• Health Canada’s review of the available information found a link between the use of Keytruda or Tecentriq and the risk of aplastic anemia. The review also found that the risk applied to all members of the ICI drug class.

• Health Canada is working with the manufacturers to update the product safety information in the Canadian product monographs (CPMs) for Keytruda and Tecentriq, as well as for the other products in the ICI drug class that are not currently labelled for this risk (Bavencio, Imfinzi, Jemperli and Libtayo), to include the risk of aplastic anemia. Health Canada will also inform healthcare professionals about this update through a Health Product InfoWatch communication.

Keytruda and Tecentriq belong to a class of drugs called ICIs. They work with the immune system to help control the growth of cancer cells. Other members of this drug class authorized for sale in Canada include Bavencio (avelumab), Imfinzi (durvalumab), Jemperli (dostarlimab), Libtayo (cemiplimab), Opdivo (nivolumab) and Yervoy (ipilimumab).

In 2021, Health Canada completed a safety review that found a possible link between Opdivo, used alone or in combination with Yervoy, and the risks of autoimmune hemolytic anemia, aplastic anemia, cytokine release syndrome and tumor lysis syndrome. The CPMs for Opdivo and Yervoy were updated to include these risks at that time.

In 2023, Health Canada reviewed the potential risk of aplastic anemia with the use of Keytruda or Tecentriq. The safety review was triggered by safety information received from the manufacturers and published in the medical literature.

Aplastic anemia is a condition in which the body stops producing enough new blood cells, with signs and symptoms including tiredness, prolonged bleeding, and an increased risk for infections.

• Keytruda and Tecentriq are prescription drugs authorized for sale in Canada to treat different types of cancer.

• Keytruda has been marketed in Canada since 2015. It is currently available as a solution for infusion into a vein (intravenous).

• Tecentriq has been marketed in Canada since 2017. It is currently available as a concentrate solution for intravenous infusion.

• Health Canada reviewed information provided by the manufacturers, and from searches of the Canada Vigilance database^a, the World Health Organization’s adverse drug reaction database^b and the scientific literature.

• Health Canada reviewed 12 cases (1 Canadian and 11 international) of aplastic anemia in patients receiving Keytruda. Of those 12 cases, 1 was found to be probably linked to the use of Keytruda, 9 (1 Canadian) were found to be possibly linked, 1 was unlikely to be linked and 1 could not be assessed.

• Health Canada reviewed 2 international cases of aplastic anemia in patients receiving Tecentriq. Both cases were found to be possibly linked to the use of Tecentriq.

• Health Canada also reviewed 9 articles published in the scientific literature reporting cases of aplastic anemia with the use of Keytruda or Tecentriq. The evidence reviewed further supports the link between the risk of aplastic anemia and the use of Keytruda or Tecentriq.

• Based on the available evidence, including a biological mechanism to explain how ICIs could lead to aplastic anemia and the findings of Health Canada’s previous review for Opdivo, used alone or in combination with Yervoy, it was concluded that the risk of aplastic anemia applies to all members of the ICI drug class.

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 Keytruda and Tecentriq 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.

2. World Health Organization’s adverse drug reaction database