Imatinib is a tyrosine kinase inhibitor used in the treatment of haematological malignancies (specifically Philadelphia chromosome positive chronic myeloid leukaemia (CML) or acute lymphoblastic leukaemia (ALL)), Kit (CD117) positive gastrointestinal stromal tumours and other malignancies. Imatinib inhibits signalling and proliferation of cells driven by dysregulated platelet-derived growth factor receptor (PDGFR) and ABL kinase activity.
Inadequately treated haematological malignancies in pregnancy may be associated with increased risks for miscarriage, thromboembolism, fetal growth restriction, preterm birth (and associated sequelae) and perinatal mortality, in addition to severe maternal illness and, potentially, death.
Data regarding imatinib use in human pregnancy are limited to retrospective case reports and case series describing approximately 290 pregnancies, 196 of which were exposed in the first trimester. No controlled epidemiological studies have assessed the risk of congenital malformation, miscarriage, intrauterine death, low birth weight, preterm delivery, neonatal complications or adverse neurodevelopmental outcomes following in utero imatinib exposure.
Both animal studies and human case reports have described malformations in fetuses exposed to imatinib during organogenesis. Certain specific anomalies (combinations of exomphalos, renal agenesis, scoliosis and hemivertebrae) have been reported in four infants in the published literature and in one infant reported retrospectively to UKTIS. Although duplicate reporting of the same malformed child is possible, and investigation for a genetic cause was not undertaken for any of these cases, further investigation is warranted to determine if these reports signal a pattern of malformation attributable to in utero imatinib exposure.
Cases of miscarriage, stillbirth, preterm delivery, intrauterine growth restriction/low birth weight and neonatal complications following in utero imatinib exposure have been described in the literature. Due to the lack of controlled studies and the potential for these outcomes to be influenced by the underlying conditions for which imatinib is used to treat, it is not currently possible to assess the direct impact imatinib use in pregnancy may have on these outcomes.
The potential teratogenicity of imatinib and other tyrosine kinase inhibitors requires that their use in pregnancy be carefully considered against the need to prevent deterioration of the maternal disease. Patients wishing to interrupt therapy to become pregnant should also be informed of the risk of relapse, even where complete molecular remission was achieved, and of the possibility of a suboptimal response on restarting therapy. Imatinib should only be used during the first trimester of pregnancy where benefits of treatment clearly outweigh the potential risk of congenital malformation and where these risks and benefits have been fully discussed with the patient.
Due to the lack of data, additional fetal monitoring for structural malformation and growth may be warranted on a case-by-case basis. Other risk factors may also be present in individual cases, which may independently increase the risk of adverse pregnancy outcome. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments.
This is a summary of the full UKTIS monograph for health care professionals and should not be used in isolation. The full UKTIS monograph and access to any hyperlinked related documents is available to NHS health care professionals who are logged in.
If you have a patient with exposure to a drug or chemical and require assistance in making a patient-specific risk assessment, please telephone UKTIS on 0344 892 0909 to discuss the case with a teratology specialist.
If you would like to report a pregnancy to UKTIS please click here to download our pregnancy reporting form. Please encourage all women to complete an online reporting form.