IMATINIB AND PREGNANCY RISK

Women who are taking imatinib (Gleevec, Novartis) for the treatment of chronic myeloid leukemia (CML) are at high risk for fetal congenital malformation if they become pregnant and should be counseled to terminate the pregnancy if it is unplanned, a retrospective analysis suggests.

Alternatively, if a pregnancy is planned, physicians need to achieve as deep a molecular response as possible for 18 to 24 months, after which treatment should be discontinued, ideally 3 months before conception and throughout the pregnancy itself, the same analysis suggests.

"It's always a tricky situation," Mitul Modi, MD, resident in pathology, Pennsylvania Hospital,  Penn Medicine, University of Pennsylvania, Philadelphia, told Medscape Medical News.

"But we found that out of 10 women who continued with imatinib during pregnancy despite counseling, 7 had a normal delivery, 1 was very preterm, and there were 2 major congenital malformations — 1 omphalocele and 1 craniosynostosis — so we now recommend that if a patient starts to lose their response during pregnancy, they be treated with another CML option and then restarted on imatinib immediately after delivery," Dr Modi added.  

Dr. Modi was among the top eight finalists for the platform oral paper session held during the American Society for Clinical Pathology (ASCP) 2017 Annual Meeting.

Study Details 

Dr Modi noted that the study looked at a total of 2008 patients with CML treated at a single center between January 1998 and December 2014. Of this cohort, 5.1% of patients were included in the current analysis. This included male patients receiving imatinib whose partners became pregnant while they were on the drug, as well as female patients who became pregnant.

Before the approval of imatinib in 2002, patients with CML would be treated with a non–tyrosine kinase inhibitor (TKI)–based therapy, including hydroxyurea, interferon alfa, or leukapheresis, the team noted.

After approval of imatinib, most patients received the approved dose of 400 mg/day, the investigators note.

"All the female partners of the CML [male] patients had normal full-term deliveries without any congenital malformations," they report.

Among the female patients, 19 became pregnant while receiving imatinib. Of these, 10 elected to continue  treatment, while the others decided to terminate the pregnancy after counselling. 

As mentioned above, from these 10 continued pregnancies there were 1 very preterm birth and 2 congenital malformations. 

"The management of CML during pregnancy poses a therapeutic dilemma because of the potential teratogenic effect of therapy, yet discontinuation of the drug is associated with loss of cytogenic and molecular response," the researchers observe.

"Although there are reports of patients who continue therapy throughout pregnancy with no problems for the baby, we do not recommend using a TKI at all during pregnancy," they conclude.

Dr Modi stressed, however, that when a non-TKI treatment is used during pregnancy, women need to be monitored monthly or bimonthly to determinate if they are losing their response to therapy.

If they are, restarting imatinib may be considered again, but only in consultation with a hematologist.