Management of chronic myeloid leukemia during pregnancy among patients treated with a tyrosine kinase inhibitor: a single-Center experience

Abstract

Tyrosine kinase inhibitors (TKIs) are teratogenic. Chronic myeloid leukemia (CML) is increasingly identified in younger patients who wish to conceive, the management of CML during pregnancy is challenging. We reviewed 51 pregnancies involving 37 patients (30 women, 10 with >1 pregnancy and 7 men) who were either diagnosed with CML during pregnancy or receiving TKI at the time of conception. Ten women were involved in >1 pregnancies. Fifteen women were diagnosed with CML during pregnancy: 10 were treated with hydroxyurea (n = 5), interferon-alfa (n = 3), leukapheresis (n = 1), or nilotinib (n = 1). There were 14 (82%) healthy babies born on term including 2 sets of twins, 2 spontaneous miscarriages (12%), and 1 elective abortion (6%). Within 1 month of delivery or abortion, all women started TKI and achieved MR4.5 (n = 6) and MMR (n = 8) within 3–48 months. One patient, treated with interferon during pregnancy, died of blast phase within 2 months. Four of the 14 remaining women later conceived 5 other pregnancies while on TKI (3 unplanned, 2 planned). Twenty-six patients (7 men; 19 women) conceived while on TKI, with a total of 36 pregnancies. Fifteen women had 20 unplanned pregnancies while receiving TKI and discontinued immediately upon recognition of pregnancy. The median time of TKI exposure was 3 weeks (range, 2–11). Five pregnancies ended in miscarriages and 3 in elective abortion. All 7 men fathered 7 full-term healthy babies. Of 20 babies born to men and women (including one set of twins), 1 had minor abnormality. Seven women lost their responses during pregnancy but at the end of pregnancy all but 2 resumed TKI and regained responses. Seven women involved in 9 planned pregnancies discontinued TKI prior to conception for a median of 4 months (range, 1–20); 3 lost responses during pregnancy. Only 5 patients resumed therapy after delivery. Outcomes were 6 full-term healthy babies, one premature, and two miscarriages. Conception among CML patients while on TKI could be uncomplicated. While patients may lose response following treatment interruption, nearly all regain response upon resuming therapy. Therapy during pregnancy is rarely needed.

Keywords:

• CML
• TKI
• pregnancy
• spontaneous abortion
• malformation

Disclosure statement

J. Cortes has received consultancy fees from Novartis, Pfizer, Takeda, and Sun Pharma; research funding from BMS, Novartis, Pfizer, Takeda, Sun Pharma and has served on speakers bureaus for BMS, Novartis, Pfizer, Takeda.

H. Kantarjian has received consultancy fees and honoraria from Abbvie, Amgen, Daiichi-Sankyo, Novartis, Pfizer, Adaptive Biotechnologies, Apptitude Health, Bioascend, Delta Fly, Janssen Global, Oxford Biomedical and Takeda; Received grants from AbbVie, Amgen, Ascentage, BMS, Daiichi-Sankyo, Immunogen, Jazz, Novartis, Pfizer, and Sanofi and has served on speakers bureaus for Actinium.

F. Ravandi has received consultancy fees from BMS and has served on speakers bureaus for BMS and Novartis.

R. Assi, M. Keating, N. Pemmaraju, S. Verstovsek, G. Borthakur, E. Jabbour, G. Garcia-Manero and J. Dahl declare no competing interests.

Author contributions

JC, HK and RA designed the study. JC and RA wrote the manuscript. All authors provided study materials or patients, contributed to collection and assembly of data, data analysis and interpretation, and reviewed and approved the final draft of the manuscript.

Ethics approval

This analysis was conducted under a retrospective chart review approved by the Institutional Review Board (IRB) at MD Anderson Cancer Center and registered in clinicaltrials.gov (NCT00816114). A waiver of informed consent was granted by the IRB for this study.

Data availability statement

Not available for public use.

Additional information

Funding

This study was supported by University of Texas MD Anderson Cancer Center Support Grant [P30 CA16672] and award P01 CA049639 (PI, Dr. Richard Champlin) from the National Cancer Institute (NCI).