Experience with dasatinib and nilotinib use in pregnancy

Area of Science:

• Oncology
• Pharmacology
• Reproductive Medicine

Background:

• Chronic myeloid leukemia (CML) treatment during pregnancy poses significant challenges.
• Dasatinib and nilotinib are tyrosine kinase inhibitors (TKIs) used for CML, including resistant cases.
• Animal studies indicate potential teratogenicity and mortality with dasatinib and nilotinib exposure during organogenesis.

Purpose of the Study:

• To review existing human pregnancy data for dasatinib and nilotinib use in CML patients.
• To evaluate the relationship between TKI exposure (dose, duration, trimester) and patient/fetal outcomes.
• To inform clinical practice regarding CML management in pregnant individuals.

Main Methods:

• Systematic review of human pregnancy case reports and studies involving dasatinib or nilotinib.
• Analysis of reported patient demographics, CML characteristics, TKI treatment details, and pregnancy outcomes.
• Assessment of fetal outcomes, including malformations and survival, in relation to maternal TKI exposure.

Main Results:

• Limited human data suggests dasatinib and nilotinib may pose risks to the fetus.
• No definitive correlation was established between TKI dose, duration of exposure, trimester of use, and adverse patient or fetal outcomes.
• Significant fetal harm, including skeletal malformations and mortality, was observed in animal studies.

Conclusions:

• Healthcare providers must counsel women of childbearing potential with CML about the potential risks of dasatinib and nilotinib during pregnancy.
• Current evidence does not allow for definitive conclusions on dose-response or trimester-specific risks in humans.
• Alternative CML management strategies, such as interferon alfa or leukapheresis, alongside TKI discontinuation, may be safer during pregnancy.