TOPLINE:
Immune checkpoint inhibitors (ICIs) are now widely used immunotherapies for many cancers, but their use in pregnancy is discouraged because of the lack of safety data. This first-of-its-kind study of WHO’s pharmacovigilance database by French researchers found no adverse pregnancy, foetal, or newborn outcomes when ICI is given as monotherapy vs other anticancer agents. The study did find excess preterm birth when two ICIs are given together as combination therapy.
METHODOLOGY:
- This cohort study was designed to assess the risk for pregnancy-, foetal- and/or newborn-related adverse outcomes linked to ICIs vs other anticancer agents given during pregnancy.
- The ICIs were blockers of three protein targets on immune cells: programmed cell death 1 (PD1) or its ligand or cytotoxic T-lymphocyte–associated protein 4 (CTLA4).
- The outcomes were 45 individual maternofoetal and newborn adverse outcomes across the WHO pharmacovigilance database known as VigiBase up to June 26, 2022. The database serves more than 130 countries.
- Case reports of ICI-related adverse events were compared with non-case reports associated with exposure to other anticancer agents during pregnancy in a design known as case–non-case disproportionality analysis.
TAKEAWAY:
- The analysis found 91 case reports of ICI-related adverse events vs 3467 case reports from other anticancer drugs.
- The 91 ICI case reports were most commonly linked to use in breast cancer (30.1% of reports) and chronic myeloid leukaemia (26.9% of reports).
- There were no excess case reports of maternofoetal adverse events linked to ICI use as monotherapy (vs other non-ICI anticancer agents).
- Preterm birth was nearly 14 times more common with combination therapy with two ICIs — anti-PD1 plus anti-CTLA4 — compared with other anticancer agents (reporting odds ratio, 13.87; P < .001).
- There were three case reports of maternofoetal events, possibly immune-related: Maternal antiphospholipid syndrome leading to spontaneous abortion, pneumonitis leading to neonatal respiratory distress syndrome and death, and transient congenital hypothyroidism.
IN PRACTICE:
The authors concluded, “The findings suggest that ICI use during pregnancy may be better tolerated than previously suspected…[but] due to possible rare immune-related neonatal adverse events ICI use in pregnant women should be avoided when possible, especially the anti-PD1 plus anti-CTLA4 combination.”
SOURCE:
The corresponding author is Paul Gougis, MD, of Pitié Salpêtrière Hospital, Assistance Publique–Hôpitaux de Paris, Paris, France. The study appeared in JAMA Network Open.
LIMITATIONS:
A study limitation is its retrospective observational design.
DISCLOSURES:
The study had multiple funding sources including the Fondation ARC Pour la Recherche Sur le Cancer. Several authors reported conflicts of interest from industry sources.