Conference Coverage

VIDEO: Careful TKI hiatus makes CML pregnancy possible



– The success that tyrosine kinase inhibitors have had in prolonging life and producing deep hematologic and molecular remissions in patients with chronic myeloid leukemia has led to an unexpected bonus for young women living with the disease: an opportunity to safely become pregnant and mother a child.

The approach is not yet routine and poses a level of risk to both the mother and fetus, especially because tyrosine kinase inhibitors (TKIs) are teratogenic. But with careful planning, close gestational monitoring, and with support from skilled obstetricians, the scenario of a successful pregnancy in women with chronic myeloid leukemia (CML) has now played out several dozen times at a handful of U.S. centers, Mrinal S. Patnaik, MD, said in a talk at the conference held by Imedex.

“We make it clear that this is experimental and is associated with risk, and we share the data [from case reports]; but if the woman wants to go forward,” a protocol now exists “to successfully get them to pregnancy,” said Dr. Patnaik, a hematologist oncologist at the Mayo Clinic in Rochester, Minn.

At Mayo alone, upwards of 20 women with CML have been successfully shepherded through pregnancy, he said in a video interview.

The prospect for a planned pregnancy is reserved for women with their CML well controlled for at least 2 years using a TKI, most often imatinib (Gleevec). In addition to being under complete hematologic control, the candidate patient must also show a deep molecular response, which means a blood level of the BRC-ABL tyrosine kinase that drives CML at least 4 or 4.5 logs (10,000-50,000-fold) below pretreatment levels or molecularly undetectable.

The patient then monitors her ovulatory cycle and stops her medication at the time of ovulation, attempts conception, and then monitors whether pregnancy has actually started. If it has, she needs to stay off her TKI regimen through at least the first 18 weeks of gestation, although an even longer drug holiday is preferred. If not, she resumes the medication and repeats the process later if she wants.

Once the women is pregnant and remains off her TKI regimen Dr. Patnaik and his associates closely follow the woman for signs of a molecular or hematologic relapse, although the latter are unusual. If a resurgence of CML stem cells occurs, the woman receives treatment with pegylated interferon-alpha, which is safe during pregnancy. When possible, TKI treatment remains on hold into the breast-feeding period.

During pregnancy and delivery, the patient requires careful and regular follow-up by a maternal-fetal medicine specialist and has an ongoing risk for high platelet counts causing placental blood clots, fetuses that are small for gestational age, preterm labor, premature rupture of membranes, and other complications.

“These are manageable with good obstetrical care,” Dr. Patnaik said. “We have developed a good system to work out the obstetrical complications.

“By and large we can be successful, but it requires a lot of monitoring and a lot of patient compliance with regular follow-ups,” he stressed.

In a video interview at the meeting, Dr. Patnaik discussed the approach he takes with his patients.

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