Delivery of two normal twins exposed to imatinib and nilotinib during the first trimester of pregnancy in a woman with chronic myeloid leukemia

Abstract

We report here the case of a 35-year-old woman. She was diagnosed with Philadelphia chromosome-positive chronic myeloid leukemia. Because of primary infertility, she received imatinib without contraception. Complete cytogenetic response was not obtained with 800mg/day. As a result, the patient was switched to nilotinib at 400 mg twice a day. An accidental pregnancy was identified at a term of 9 weeks while the patient was on imatinib during the first 4 weeks then nilotinib between 5th and 9th weeks of gestation. Because the patient elected to continue the pregnancy to term, nilotinib was discontinued; no further treatment was given until delivery. A follow-up with ultrasound scans was unremarkable. She successfully gave birth to female twins at 38 weeks with no malformation until 13 months post- partum. This experience provides a useful contribution for counselling patients exposed to nilotinib during pregnancy.

The introduction of the tyrosine kinase inhibitors TKI since 1998 indisputably advanced the clinical management of chronic myeloid leukemia CML. As a result, patients who are of childbearing age and are currently being treated with TKI now find themselves contemplating reproductive opportunities that would not have otherwise been possible. Because imatinib was teratogenic in rats, in addition to general safety concerns surrounding the use of any new drug in pregnancy and the limited data available in the public domain on the outcome of pregnancies of patients exposed to imatinib, it was strongly advised that effective contraception be used during therapy to prevent pregnancy ^[1-4]. Moreover, there is still very insufficient data on the second generation TKIs to warrant their safety in pregnant women with CML ^{[5, 6]}. We report the outcome of a patient with CML who became pregnant while receiving imatinib then nilotinib.