Impact-CML: Indian multicentric data supporting safe pregnancy and molecular control in women with chronic myeloid leukemia

Abstract

Abstract Introduction Data guiding management of tyrosine kinase inhibitors (TKI) during pregnancy in chronic myeloid leukemia (CML) are limited, especially from low- and middle-income countries (LMICs). This study was performed to describe real world outcomes in patients with pregnancy on TKIs for CML. Methodology This retrospective, multicenter study (IMPACT-CML: Indian Multicentric Pregnancy and Chronic Myeloid Leukemia Outcomes Tracking) was conducted by the Hematology Cancer Consortium India CML working group. Women of childbearing age who were on follow up between January 2017 to June 2025 and had a pregnancy while on TKIs or were diagnosed with CML during pregnancy were screened for inclusion. The primary objective was to describe obstetric outcomes, TKI discontinuation, maintenance of major molecular response (MMR) post-pregnancy and pregnancy related complications. Results A total of 478 women were screened, of whom 50 women with a median age of 25 years (IQR 22-28) were included. At the time of conception, 32/50 (64%) were already on TKIs and only 14/50 (28%) pregnancies were planned. Most women (N=45, 90%) were on Imatinib, and the rest on Dasatinib. For most women, this was the first pregnancy after the diagnosis of CML (N=32, 76.2%), ten had a previous pregnancy and data was unavailable for eight. Among 10 women with a prior pregnancy after diagnosis of CML, 6 (60%) had live births, 3 (30%) underwent medical termination (MTP), and 1 had intrauterine death (IUD). Among planned pregnancies (n=14), TKIs were discontinued by 11 (78.6%), with 7(63%) stopping pre-confirmation and 4 (36%) post confirmation of pregnancy. TKI discontinuation was further documented in 12 women during the first trimester, 11 during the second, and 8 during the third, with most stoppages lasting >2 months (92.3%, 91.7%, and 80%, respectively) in each trimester. An overlap with planned cases was not separately defined. Five patients were transitioned to interferon prior to or during pregnancy. Baseline values of BCR::ABL International Scale (IS) (within six months of pregnancy) were available for 33/50 (66%), with a median value of 0.14% (IQR 0.01–0.75), of whom 15 (45.5%) were in MMR or better. Sequential values were available for 13 patients in the first trimester (median 0.25%, Range 0-35), 13 in the second (median 0.26%, Range 0-10), and 9 in the third (median 0.16%, Range 0.01 to 2.09). Pregnancy outcomes were available for 43 women, of whom 25/43 (58.13%) had a live birth (20 term deliveries, 5 preterm) with median birth weight of 2.50 kg (IQR 1.85–2.95, Range 1.12 to 3.50 Kg). Medical termination of pregnancy was opted by 13 patients (13/43, 30.2%), of which 9 (9/13, 69%) were physician advised. One instance each of pregnancy induced hypertension and post-partum hemorrhage were documented. Median gestational age at delivery was 36.5 weeks (IQR 15–37), including term births and terminations. Among patients who remained on TKIs throughout the first trimester (n=35/47 [74.4%]), excluding 3 without outcome data), most (n=18, 51%) achieved term or pre-term delivery, 13 (37%) underwent MTP and 5 (10%) had spontaneous abortions. No congenital malformations were reported in live births, including those who continued TKIs through the first trimester. Post-pregnancy molecular data were reported in 23/50 (46%) patients, with median BCR::ABL IS value of 0.11% (0.01–0.70), with 11 (47.8%) in MMR. There was no statistically significant association between TKI discontinuation and post-pregnancy BCR::ABL IS levels (p=0.2368). Preterm delivery was significantly correlated with unplanned pregnancy (p=0.016) and lack of molecular testing before conception (p=0.024). After a median follow-up of 74.07 months (IQR 41.11–140.70) from CML diagnosis, all patients were alive. Molecular data were available for 48/50 (96%), with median BCR::ABL IS value of 0.01 (IQR 0.00–1.17). Conclusions In the first Indian multicentric data describing pregnancy outcomes in women with CML, we observe a high frequency of healthy live births despite early trimester TKI exposure and preserved long term disease control. Rates of spontaneous abortions were not higher than published data in the general population, highlighting the potential to reduce physician-advised MTPs in this setting. Our data indicates potentially safe outcomes in pregnant women with CML with pre-conception planning and subsequent monitoring.