Evaluating the Safety and Efficacy of Tyrosine Kinase Inhibitors in Pregnant Patients with Chronic Myeloid Leukemia: A Comprehensive 15-Year Single-Center Study

Background and Significance

Managing chronic myeloid leukemia (CML) during pregnancy poses significant challenges due to the potential teratogenic effects of tyrosine kinase inhibitors (TKIs). Planned pregnancies, stable disease control before conception, and close monitoring are critical for optimizing results. This study provides an in-depth analysis of maternal and fetal outcomes with long-term follow-up in CML patients treated with TKIs over a 15-year period at King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh, Saudi Arabia.

Study Design and Methods

This analysis reviewed records from prospectively collected data of 425 patients from an IRB-approved CML database from 2005 to 2020. Fifty-one patients were identified with 99 pregnancies. Key metrics evaluated include patient demographics, treatment regimens, pregnancy outcomes, and maternal-fetal health. Statistical methods included descriptive statistics and Kaplan-Meier survival estimates for overall survival (OS) and progression-free survival (PFS).

Results

A total of 51 patients with a mean age at diagnosis of 28.04 years (ranging from 15 to 41 years) were included in the study. During pregnancy, the mean age was 32.34 years (ranging from 21 to 47 years). The average number of pregnancies per patient was 1.91, with the majority being unplanned (95), while 4 were planned.

Following postpartum TKI resumption, patients achieved major molecular responses (MR4.5) in 53% and major molecular responses (MMR) in 27% of cases. Overall pregnancy outcomes included 9 miscarriages, one elective abortion, and 82% healthy live births, which included one set of twins. Ninety-six percent of pregnancies were unplanned as the patients continued using their TKIs until confirmed pregnancy (average exposure 4-6 weeks).

In terms of fetal outcomes, 82% of the pregnancies resulted in healthy babies. The overall miscarriage rate was 5.3%, which is comparable to the general population. Common patient pregnancy complications included 8 gestational diabetes mellitus (GDM), 4 losses of response to therapy, and one postpartum hemorrhage. Fetal complications included 9 spontaneous abortions, 4 intrauterine growth restrictions (IUGR), and no congenital anomalies.

Conclusion

This study demonstrates and offers valuable insights into the management of CML patients with unplanned pregnancies and exposure to TKIs in the early first trimester, leading to favorable maternal and fetal outcomes. TKI exposure during early pregnancy was not associated with unfavorable outcomes.

Saad:Sanofi: Consultancy; Kite: Consultancy. Alfayez:Astellas: Consultancy, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Biologics: Honoraria, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Johnson & Johnson: Consultancy, Honoraria, Research Funding, Speakers Bureau; Abbvie: Consultancy, Honoraria, Research Funding, Speakers Bureau. Alzahrani:Sanofi: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Other: All authors received support for third-party writing assistance, furnished by Akshaya Srinivasan, PhD, CMPP, of Nucleus Global, an Inizio company, and funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland., Research Funding; Novartis: Consultancy, Honoraria, Research Funding; CSL Behring: Consultancy, Honoraria, Research Funding; Sobi: Consultancy, Honoraria, Research Funding; Pfizer: Research Funding.