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Pregnancy Outcomes among Patients with Chronic Myeloid Leukemia Treated with Dasatinib

Jorge Cortes, Susan O’Brien, Patricia Ault, Gautam Borthakur, Elias Jabbour, Brigid Bradley-Garelik, Krisztina Debreczeni, Daniel Yang, David Liu and Hagop Kantarjian

Abstract

Dasatinib has been shown in non-clinical studies to cause fetal toxicities in animals, but the effect of exposure during conception and pregnancy in humans is not known. Despite the requirement for contraception while on therapy with dasatinib, occasional pregnancies have been reported. The current study and post-marketing data report the outcomes of pregnancies occurring among 16 patients (8 females and 8 males) who received dasatinib therapy. Among the 8 female patients found to be pregnant while on dasatinib therapy, induced abortion was reported in 3 cases: 2 due to patient decision and 1 for unknown reasons. Two cases of spontaneous abortion were reported. The first was at 8 weeks gestation in a 38-year-old patient (G1P1) with a history of tobacco use. Birth defects of the fetus were not reported; though it is unknown if an autopsy was performed. The other spontaneous abortion was reported at 9 weeks gestation in a 33-year-old patient (G3P3) taking dasatinib for over 2 years. The medical history of this patient includes tobacco and alcohol use. Of the 3 deliveries, one patient had a normal healthy infant. The second patient (age: 29 years, G2P2) delivered a healthy infant by Caesarean section at 7 months gestation (reason for Caesarean section unknown). This patient received dasatinib 140mg/day for approximately 4 months, but was ‘lost to follow up’ for 2 months and study drug compliance was unknown. Upon her return, the patient had a positive pregnancy test with an estimated gestation of 4 weeks. The infant was reported as ‘small for date’ but without obvious birth defects. Apgar scores were also unknown for this infant. In the final case, a patient on dasatinib 100mg/day for approximately 5 months was identified as pregnant (G0P0) at 21 weeks of gestation. The estimated delivery date has not yet occurred at the time of writing, but the pregnancy course has been normal. Among 8 male patients treated with dasatinib with partners becoming pregnant while on treatment, normal newborns were reported for 7 cases, with the outcome of the other case unknown. All male patients remained on treatment during and after the pregnancies. In 1 case, the mother experienced pre-eclampsia but delivered a healthy newborn at 37 weeks, without birth defects or neonatal complications. In summary, although the limited data reported in this study did not show evidence that dasatinib treatment has a negative impact on pregnancy (for the mother or fetus), patients receiving dasatinib should be advised to practice adequate contraception.

Table 1. Outcome of Female Patients Electing to C regnancy

Duration of Fetal Exposure to Dasatinib Fetal Outcome Maternal Outcome Dasatinib Dose* Duration of Dasatinib Therapy
* at time of onset
Pt D5 weeks8wk spontaneous abortionno adverse reaction reported180 mg/dayapproximately 9.5 months
Pt E9 weeks9wk spontaneous abortionno adverse reaction reported100 mg BID30 months
Pt F7 weeksnormal healthyno adverse reaction reported140 mg/dayapproximately 15 months
Pt Gunknown“small for date” – healthy newbornC-section at 7 months140mg/dayapproximately 4 months
Pt H21 daysto be determined100mg/day5 months