Complexine kinase inhibitors (TKI) are contraindicated in women with proposed pregnancies and in the first trimester because of the increased incidence of miscarriage and fetal anomalies. The safety of TKI in mid- and late pregnancy is not known. it is unknown whether TKI affects male fertility or increases the rate of miscarriage or fetal abnormalities in male female partners taking TKI.
The use of TKI in early pregnancy is strongly advised against due to the risk of fetal malformations; there is no consensus on the optimal monitoring and management of CML in pregnancy. Monthly monitoring of BCR-ABL1 by qPCR is generally recommended, and treatment is initiated if BCR-ABL1 increases to ≥1.0%.
Our approach is as follows: ● Early Pregnancy – For women who require treatment in early pregnancy, we recommend treatment with leukapheresis and/or interferon rather than TKI. Interferon is safe during pregnancy; some experts believe hydroxyurea is safe in this setting. Low-dose aspirin and/or low-molecular-weight heparin may be used for thrombocythemia.
● Late pregnancy – In mid- or late pregnancy, the potential benefits of TKI for the mother must be weighed against the risks to the fetus; interferon, leukapheresis, or other approaches may be preferable in this situation.
● Care – Women should not breastfeed while taking a TKI because it can enter human breast milk and may impair the growth and/or development of the infant.
● Female patients A study of 180 women exposed to imatinib during pregnancy reported that half of the pregnancies with known outcomes were normal, but 10% of fetal abnormalities ended in spontaneous abortion. Of the 46 women treated with dasatinib during pregnancy, one-third delivered normal babies, but the incidence of elective or spontaneous abortion was 39% and 17%, respectively, 11% had abnormal pregnancies, and 15% had fetal abnormalities. Among men treated with dasatinib, 91% of the 30 female partners delivered normal babies at birth. Of the 16 women treated with bosutinib during pregnancy, 10 had a known outcome; of these, 5 had a full-term vaginal delivery, 1 had a live birth of unknown outcome, 3 had an induced abortion, and 1 had a spontaneous abortion.
● Male patients Among the 17 men treated with bosutinib, 14 pregnancies had known outcomes; nine patients had full-term healthy infants, four had abortions, and one had a spontaneous abortion.
Of course, it would be better to discontinue the drug after the slow granules can meet the criteria for discontinuation. For more information on how to discontinue chronic granules, please refer to the previous section.