Chronic Myelogenous Leukemia: Pregnancy in the Era of Stopping Tyrosine Kinase Inhibitor Therapy
Cette étude passe en revue les essais cliniques évaluant l'intérêt d'arrêter une thérapie à base d'inhibiteurs de tyrosine kinase chez les patientes atteintes d'une leucémie myéloïde chronique et désirant avoir un enfant ultérieurement, puis analyse les effets de 5 traitements par inhibiteurs de tyrosine kinase sur la fertilité
Approximately 28% of patients diagnosed with chronic myelogenous leukemia (CML) in 2018 will be younger than 49 years old,1 making it important for clinical care teams to be aware of options for family planning. The last 5 years of clinical research on this disease have seen a shift from new drug development (a total of five tyrosine kinases [TKIs] are now licensed, three for first-line use) to determining which patients can safely stop therapy.2-8 Fortunately for men, TKI therapy does not seem to have a deleterious affect on fertility, and there is not an increase in miscarriage rates or birth defects in their female partners.9,10 However, in women who take TKIs while pregnant, the incidence of stillbirth, miscarriage, and fetal malformations seems higher than that found in the general population, and strong recommendations have been made to avoid pregnancy while receiving TKI therapy.9,10 Recent reports suggest that approximately 40% of patients who have achieved a complete molecular remission, also termed MR4.5, can safely stop therapy without having disease recurrence,2-8 and questions regarding pregnancy are being asked with increasing frequency. Such questions include (for women): What kind of response do I need before I can stop TKI therapy? Does TKI therapy directly affect oocytes, or sperm if my male partner is taking a TKI? Should in vitro fertilization (IVF) be considered to try to minimize the time between stopping therapy and getting pregnant? What would happen if my polymerase chain reaction (PCR) result increased while I am pregnant, and what treatment is available then? What is the likelihood of responding again to TKI therapy after the baby is born? This review summarizes the results of ongoing “stop therapy” trials, what is known abut the effects of TKIs on oogenesis and spermatogenesis, and what strategies can be used for women who want to get pregnant. Solutions will involve partnerships among the patient, her oncology care team, and her obstetrician. (...)