Commentaries

Chronic Myeloid Leukemia and Pregnancy

Termination is not mandated for pregnant women receiving treatment for chronic myeloid leukemia (CML), according to a presentation at the 2018 Great Debates and Updates in Hematologic Malignancies meeting (April 13-14, 2018, New York, NY).

Marlise Luskin, MD, MSCE, presented information on the risk of TKI therapy on pregnancy in patients with CML and what to do for patients who become pregnant while receiving treatment, as well as those who desire to conceive.

Dr Luskin explained that the fundamental issues in CML and pregnancy are that for young women with CML, no TKI has been established as safe for a developing fetus. Pre-clinical studies have shown that TKIs are associated with embryo-fetal toxicity.

“For obvious reasons, no prospective clinical trials have collected data on pregnancy outcomes in women exposed to TKIs”, said Dr Luskin, “although several case series have been presented.” She reported that the largest study reported 180 pregnant women who were exposed to imatinib, generally in the early trimester before pregnancy was recognized. Normal live births were reported in 50% of the pregnancies with known outcomes, 14% ended in spontaneous abortion, and 10% reported with fetal defects or congenital anomaly.

Dr. Luskin explained the fetal abnormalities reported included skeletal malformations—cleft palate, premature closure of skull sutures, scoliosis, craniosynostosis, and absent hemivertebrae—as well as effects on the renal, respiratory, and gastrointestinal systems. She explained that these reports are retrospective, so it is impossible to define the exact correlation between timing and dose of TKI exposure and abnormalities.

In patients with an established pregnancy, termination is not mandated. Dr. Luskin defined that the factors to consider in these patients are if the pregnancy was desired, the stage of the pregnancy, and stage of the disease. If the patient decides to pursue the pregnancy, the patient and fetus should be closely monitored with maternal-fetal medicine. Cessation of TKI therapy should be discussed with risk vs benefit for the patient and fetus. Reintroduction of TKI therapy should be considered only in setting of progression to advanced phase disease or lack of success with other treatment options, with careful counseling.

Dr Luskin revealed that the standard recommended treatments for pregnant women with CML are observation in chronic phase patients with no extreme cytoses and leukopheresis in chronic phase patients with leukocytosis or thrombocytosis. In patients with pregnancy risk C, interferon therapy is suggested and has shown safety in the 2nd and 3rd trimesters, although pegylated interferon is cautioned due to accumulation of polyethylene glycol. Hydroxyurea is considered a possible treatment in some cases, but is recommended to be avoided if possible, as it is possibly teratogenic.

In patients who are not pregnant, fertility counseling is recommended at CML diagnosis. Dr. Luskin explained that the patient should be assessed for desire for fertility, currently or in the future, and explained the risks of TKI exposure to the fetus. If fertility is desired, options for fertility can be discussed, such as fertility preservation prior to treatment and fertility during TKI treatment interruption.

Dr Luskin concluded her presentation by illustrating that TKI discontinuation without deep remission carries risks. She presented results that among nine female patients in complete hematologic remission (CHR) who interrupted therapy, five in CHR at the time of treatment interruption eventually lost CHR and six experienced an increase in Ph+ metaphases.

In patients with excellent control, stopping trials is increasingly accepted, but patient selection is important. Most patients with modest control will not meet the standard criteria for TKI stopping trial during period of desired fertility, Dr Luskin concluded.—Janelle Bradley

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