BCR::ABL1 Tyrosine Kinase Inhibitors During Pregnancy, a Disproportionality Analysis of Vigibase

Tyrosine kinase inhibitors (TKIs) targeting BCR::ABL1 have greatly improved the survival of patients with chronic myeloid leukemia (CML), and their teratogenicity appears as an important factor for individuals of childbearing potential. This study aims to investigate pregnancy and fetal/newborn adverse outcomes resulting from exposure to BCR::ABL1-TKIs during pregnancy. For this disproportionality analysis, we used the WHO's global VigiBase up to January 2024, and included reports involving pregnancy, antineoplastic treatment during pregnancy, and cancer. The exposure group consisted of reports mentioning BCR::ABL1-TKIs at any time during pregnancy. The primary outcome was the reporting odds ratio (ROR) of maternal-fetal complications in the BCR::ABL1-TKIs group compared to other anticancer treatments. The analysis included 3,389 reports (TKI = 969; other = 2,420). In the BCR::ABL1-TKI-exposed group, the mean age was 28.9 years, and 724 patients (92.2%) were treated for CML. BCR::ABL1-TKIs were mainly imatinib (n = 642, 66.3%), nilotinib (n = 218, 22.5%), and dasatinib (n = 127, 13.1%) reported without other non-TKI anticancer agents(92.3%). Compared to other anticancer drugs, overreported outcomes with TKIs included hydrops fetalis (ROR = 13 [95%CI = 1.5-110], P = 0.009), polyhydramnios (ROR = 5 [1.3-20], P = 0.02), and threatened preterm labor (ROR = 10 [1.1-90], P = 0.03). When analyzing specific molecule effects, hydrops fetalis (ROR = 27 [5.4-130], P = 0.001) and polyhydramnios (ROR = 13 [3.3-54], P = 0.004) were overreported with dasatinib. In this large cohort of 969 individuals exposed to TKIs during pregnancy, dasatinib use was associated with most BCR::ABL1-TKI-specific toxicities and should be avoided during pregnancy. Fewer or no adverse events were overreported with imatinib and nilotinib.