Disease outcomes for patients with chronic myeloid leukemia (CML) have drastically improved since the introduction of tyrosine kinase inhibitors (TKIs).1 However, the teratogenicity of these agents poses considerable challenges for patients who are pregnant when diagnosed with CML and for CML patients who conceive or wish to become pregnant while receiving TKI therapy.1
In a review published in April 2023 in Current Hematologic Malignancy Reports, Ellin Berman, MD, a hematologic oncologist at Memorial Sloan Kettering Cancer Center in New York, noted the dearth of guidelines regarding treatment strategies for these patients.2
Although all TKIs should be avoided in the first trimester of pregnancy, as Dr Berman wrote,some study results indicate that it may be safe to stop TKI therapy before a planned pregnancy in patients who have achieved a stable deep response.3 Additional findings suggest that the lowest rates of placental transfer may occur with nilotinib and imatinib.4
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To gain further insights into treatment considerations for these patient groups, we interviewed Wendy Stock, MD, the Anjuli Seth Nayak Professor of Medicine and director of the Leukemia Program at the University of Chicago, and Julie R. Gralow, MD, FACP, FASCO, executive vice president and chief medical officer of the American Society of Clinical Oncology (ASCO).
What are some of the main challenges that can affect family planning and pregnancy in patients with CML?
Dr Stock:Due to the teratogenic risk of TKI therapy, pregnancies in patients with CML must be carefully planned, and alternative treatments or observation during pregnancy with TKI discontinuation is essential for women with CML who wish to become pregnant.
Dr Gralow: The average age of diagnosis of CML is about 65 years, and there are about 9,000 cases a year diagnosed in the US.5 With treatment, the survival rate can be quite high — about 1300 deaths per year are due to CML in the United States.5 Dealing with family planning and pregnancy in CML affects few patients — but for those patients, it is very important.
Imatinib, dasatinib, nilotinib, and other TKIs are highly effective targeted therapies approved for the treatment of CML when the disease is in the chronic phase. These drugs should be avoided during pregnancy, especially during the early stages of pregnancy, and it is recommended that they also be avoided during breastfeeding.
The immunotherapy drug interferon was previously commonly used in the treatment of CML before the availability of the targeted agents. It is not commonly used now, but it is safe to use during pregnancy and is sometimes still used in this setting.6
Chemotherapy can also play a role in treating CML. Bone marrow transplantation can be recommended in the treatment of CML, especially when it cannot be controlled by the TKIs, but this has become less common. It is clearly more toxic than the targeted drugs, likely leads to a higher chance of future infertility, and is not safe during pregnancy.
