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. 2025 Jan 1;131(1):e35611.
doi: 10.1002/cncr.35611. Epub 2024 Oct 30.

Outcomes of pregnancy in patients with chronic myeloid leukemia in the era of tyrosine kinase inhibitors

Takeshi Kondo  1 , Eri Matsuki  2 , Tomoiku Takaku  3   4 , Naoki Watanabe  4 , Chikashi Yoshida  5 , Masaya Okada  6 , Kazunori Murai  7 , Takashi Kodama  8 , Naoto Takahashi  9 , Shinya Kimura  10 , Itaru Matsumura  11 ; Preg‐CML/Japan Study Investigators
Affiliations

Outcomes of pregnancy in patients with chronic myeloid leukemia in the era of tyrosine kinase inhibitors

Takeshi Kondo et al. Cancer. .

Abstract

Background: Young female patients with chronic myeloid leukemia (CML) often face challenges becoming pregnant due to the teratogenicity of tyrosine kinase inhibitors (TKIs).

Methods: The authors conducted a nationwide survey of female patients with CML who experienced pregnancy between 2002 and 2020.

Results: Information for 70 pregnancies in 49 patients was obtained. There were three types of pregnancies: CML onset during pregnancy (n = 9), unplanned pregnancy mostly during treatment with a TKI (n = 25), and planned pregnancy during treatment-free remission (TFR) or treatment with interferon-alpha (IFN-α) (n = 36). The median duration from CML diagnosis to pregnancy in patients with planned pregnancy was significantly longer than that in patients with unplanned pregnancy (10.6 years vs. 4.1 years, p < .001). In 48 pregnancies that resulted in childbirth, TFR and treatment with IFN-α were chosen in 26 and 17 pregnancies, respectively. Sustained major or deeper molecular response was observed in 18 of 26 pregnancies with TFR. The patients who fulfilled the requirements for TKI therapy discontinuation by European LeukemiaNet recommendations achieved a TFR rate of 77% in pregnancy. Treatment with IFN-α might be effective for patients who are in complete cytogenetic response or deeper response (response rate, 76%).

Conclusion: Pregnancy by TFR or treatment with IFN-α could be a safe and feasible way for patients with CML. However, a substantial duration of treatment with a TKI before conception may be needed for planned pregnancy. Planning and evaluation for pregnancy should be considered at the time of CML onset for female patients with childbearing potential.

Keywords: chronic myeloid leukemia; interferon‐alpha; pregnancy; treatment discontinuation; treatment‐free remission; tyrosine kinase inhibitor.

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Conflict of interest statement

Takeshi Kondo has received honoraria from Astellas Pharma, AbbVie, Amgen, Kyowa Kirin, Nippon Shinyaku, Ono Pharmaceutical, Otsuka Pharmaceutical, Novartis, Pfizer, and Bristol‐Myers Squibb; and consultancy fees from Otsuka Pharmaceutical. Eri Matsuki received honoraria from Novartis. Tomoiku Takaku received honoraria from Novartis, Otsuka Pharmaceutical, and Pfizer; and research funding from Bristol‐Myers Squibb, Otsuka Pharmaceutical, and ThinkCyte. Chikashi Yoshida received honoraria from AbbVie, Bristol‐Myers Squibb, Chugai Pharmaceutical, Janssen, Novartis, Nippon Shinyaku, Ono Pharmaceutical, Otsuka Pharmaceutical, Pfizer, and Takeda Pharmaceutical; and research funding from Bristol‐Myers Squibb. Naoto Takahashi received honoraria from Novartis and Otsuka Pharmaceutical; and research funding from Novartis, Asahi Kasei Pharma, and Otsuka Pharmaceutical. Shinya Kimura has received honoraria from Otsuka Pharmaceutical, Novartis, Pfizer, and Bristol‐Myers Squibb; and research funding from Otsuka Pharmaceutical, Novartis, Bristol‐Myers Squibb, Pfizer, and Ohara Pharmaceutical. Itaru Matsumura received speakers bureau fees from Takeda Pharmaceutical, Daiichi Sankyo, Pfizer, SymBio Pharmaceuticals, Astellas Pharma, Ono Pharmaceutical, Novartis, Chugai Pharmaceutical, AbbVie, Janssen, Bristol‐Myers Squibb (Celgene), Amgen, AstraZeneca, and Otsuka Pharmaceutical; research funding from Chugai Pharmaceutical, Kyowa Kirin, Sumitomo Pharma, Takeda Pharmaceutical, Astellas Pharma, Ono Pharmaceutical, Sanofi, Mitsubishi Tanabe Pharma, Nippon Shinyaku, Eisai, MSD, Asahi Kasei Pharma, AbbVie, Janssen, Taiho Pharmaceutical, Shionogi, Teijin Pharma, Nippon Boehringer Ingelheim, Nippon Pharmaceutical, Daiichi Sankyo, Nippon Kayaku, CSL Behring, Mundipharma, Ayumi Pharmaceutical, Eli Lily, Actelion Pharmaceuticals, and Amgen; and consultancy fees from Otsuka Pharmaceutical. The other authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Pregnancy pattern and outcome of pregnancy in patients with chronic myeloid leukemia (CML). There were three types of pregnancy: CML onset during pregnancy, unplanned pregnancy during the clinical course of CML and planned pregnancy with treatment‐free remission (TFR) or treatment with interferon‐alpha (IFN‐α) before conception. Times of pregnancy varied from 1 to 5. Times of childbirth varied from 0 to 3.
FIGURE 2
FIGURE 2
Treatment and response of CML during pregnancy and at delivery. (A) Cases of CML onset during pregnancy. (B) Cases with unplanned pregnancy. (C) Cases with planned pregnancy. *Treatment was changed because loss of MMR was observed. CCyR, complete cytogenetic response; CML, chronic myeloid leukemia; CHR, complete hematologic response; DMR, deep molecular response; IFN, interferon‐α; IMA, imatinib; MMR, major molecular response; PCyR, partial cytogenetic response; TFR, treatment‐free remission; TKI, tyrosine kinase inhibitor; TMA‐UD, undetectable level of BCR::ABL1 mRNA by the TMA method (equivalent to MMR or deeper response).
See this image and copyright information in PMC

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