Is Cancer Immunotherapy Safe During Pregnancy?

Immune checkpoint inhibitors (ICIs) are a form of immunotherapy among the treatments that have transformed cancer care in recent years. By making the body's immune system more effective against cancer cells, they have achieved major successes across many cancers. The remainder of this article uses "immunotherapy" as shorthand for immune checkpoint inhibitors.

However, like every new treatment, these immunotherapies carry potential risks and side effects. Safety is a particular concern during sensitive periods such as pregnancy. Their fetal and neonatal effects are not fully understood and remain under investigation. A notable new study by French researchers evaluated potential risks and safety during pregnancy, adding substantially to our knowledge.

Old Concerns, New Findings

Until now, immunotherapy during pregnancy has not been recommended because safety data are insufficient. However, this pioneering French analysis of the World Health Organization's pharmacovigilance database found no adverse effect on pregnancy, fetal or neonatal outcomes with immunotherapy alone compared with other cancer drugs. In contrast, combinations of two immunotherapies were associated with increased premature birth risk.

Study Details

This cohort study was designed to assess adverse pregnancy, fetal and/or neonatal outcomes associated with immunotherapies given during pregnancy compared with other cancer drugs.

Immune checkpoint inhibitors block three protein targets on immune cells: programmed cell death 1 (PD1), its ligand, or cytotoxic T-lymphocyte-associated protein 4 (CTLA4).

As of 26 June 2022, the WHO pharmacovigilance database VigiBase, serving more than 130 countries, had recorded 45 types of maternal-fetal and neonatal adverse outcomes. Case reports of adverse events associated with immunotherapy were compared with noncase reports involving exposure to other cancer treatments during pregnancy. This case–noncase disproportionality analysis helps assess potential risks.

Results

• The analysis compared 91 immunotherapy-associated case reports with 3467 involving other cancer drugs.
• Most of these 91 immunotherapy cases were associated particularly with breast cancer (30.1%) and chronic myeloid leukemia (26.9%).
• No increase in maternal-fetal adverse events was observed with immunotherapy alone compared with other cancer drugs.
• With combined anti-PD1 and anti-CTLA4 immunotherapy, the premature birth rate was almost 14 times higher than with other cancer drugs.
• Three reports also involved immune-related maternal-fetal events:
  1. Spontaneous miscarriage due to maternal antiphospholipid syndrome,
  2. Respiratory distress syndrome and death following pneumonia in a newborn,
  3. And transient congenital hypothyroidism.

The study suggests that immunotherapy during pregnancy may be better tolerated than previously thought. However, given possible rare immune-related neonatal adverse events, pregnant women should avoid specific approaches—particularly combined anti-PD1 and anti-CTLA4 therapy—whenever possible. Potential risks may have serious consequences, especially in more vulnerable groups.