Can Women With CML Safely Continue TKIs During Pregnancy?

Most women with chronic myeloid leukemia (CML) who received treatment with tyrosine kinase inhibitors (TKIs) and became pregnant had a normal childbirth, with no increased rate of birth abnormalities, suggesting that TKI use at conception was safe, according to an analysis of the European LeukemiaNet registry. The results were presented at the 24th Congress of the European Hematology Association by lead author Ekaterina Chelysheva, MD, PhD, from the National Research Center for Hematology in Russia.

In the era of TKIs, “patients with CML can have a near-normal lifespan,” the authors explained, making family planning an important issue for these patients. However, management of CML around conception and pregnancy is not well-defined because “cases are rare and data are scarce.”

To clarify disease management in women who become pregnant, investigators conducted a multicenter, retrospective, and prospective observational study in patients enrolled in the European LeukemiaNet registry beginning in February 2014.

The study enrolled 234 women from 13 countries who had Ph-positive CML; participants had a total of 305 pregnancies during study follow-up.

Most patients (n=217/221; 98%) had chronic-phase CML at diagnosis. Fifty patients (21%) were diagnosed with CML during pregnancy, while 184 patients (67%) became pregnant after CML diagnosis. In this group, the median time from CML diagnosis to pregnancy was 59 months (range = 1-203 months).

The authors reported that, of 257 pregnancies with known data points available, 182 (71%) were conceived while receiving TKIs. Of those, 77% were on imatinib and 23% were on a second- or third-generation TKI. Typically, TKIs were stopped early in the first trimester (at approximately 4-5 weeks of gestation), when the pregnancy was discovered.

Eighty-two women continued CML treatment during their second or third trimesters, after placental formation, or until labor, mostly with imatinib or interferon (TABLE).

Molecular response evaluations at the start of pregnancy were recorded in 249 of 305 pregnancies, and approximately one-third of patients (n=80; 32%) had deep molecular response. However, 106 patients (43%) had 2-log molecular response (BCR-ABL >1%).

Of the 305 pregnancies, the outcomes were as follows:

  • labor: 234 (77%)
  • induced abortion: 42 (14%)
  • spontaneous abortion: 21 (7%)
  • ongoing pregnancy or unknown outcome: 8 (2%)

Of a total of 187 pregnancies with complete information about term, three-quarters (n=141; 75%) occurred at full term.

Of 233 children who were born to women with complete information about their labors, congenital abnormalities were recorded in four (1.7%), including polydactyly (n=1), hypospadias (n=1), and non-closed foramen ovale of interatrial septum (n=2). “None of the abnormalities were severe or life-threatening,” the authors reported, adding that “relationship to TKI use was considered unlikely by physicians.”

“Most pregnancies in female patients with CML resulted in normal childbirth with no increased rate of birth abnormalities, in spite of TKI use at conception [and] even if treatments were mostly stopped early,” the authors reported. If TKIs were stopped, most women went on to receive alternate CML treatment throughout their pregnancies when needed.

These results “may be valuable for the development of CML treatment schemes [in women who become pregnant], particularly considering the variety of disease status,” the researchers concluded.

The study is potentially limited by the reliance on retrospectively collected information and the possibility of missing or incomplete data about patients’ pregnancies.

The authors report no relevant conflicts of interest.

Reference

Chelysheva E, Turkina A, Rea D, et al. Pregnancy outcome in female patients with chronic myeloid leukemia worldwide: analysis of 305 cases of the European Leukemia Net Registry. Abstract #S881. Presented at the 24th European Hematology Association Annual Congress, June 15, 2019; Amsterdam, The Netherlands.

TABLE. CML Therapy at Conception and During Pregnancy

Number of Patients

Percentage

CML therapy at conception (in pregnancies with available data)

257

  No therapy

74

24%

  Imatinib

141

47%

  Nilotinib

23

7%

  Dasatinib

14

5%

  Bosutinib

2

1%

  Ponatinib

2

1%

  Interferon

1

0.3%

CML therapy during pregnancy (in cases which ended in labor)

82

  Imatinib for whole pregnancy

13

16%

  Imatinib in trimester 2-3

33

40%

  Nilotinib in trimester 2-3

8

9%

  Interferon

23

28%

  Hydroxyurea

6

7%

CML = chronic myeloid leukemia

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