Managing pregnancy in chronic myeloid leukaemia

Abstract

Over the past decade, we have witnessed significant advances in knowledge of the biology and treatment of chronic myeloid leukaemia (CML). The development of molecular-targeted therapy with tyrosine kinase inhibitors (TKIs) has fundamentally changed the outcome of this disease. Treatment with TKIs is now the standard of care in patients with CML and has dramatically improved long-term survival in the majority of patients. Patients who achieve major molecular response (MMR) after 2 years of treatment with imatinib have survival rates comparable to those of the general population. The success of TKIs has led to durable molecular response and possibility of normal life expectancies, such that it is now timely to address quality of life aspects such as fertility, pregnancy and family planning. Pregnancy in CML presents specific management and therapeutic challenges for the patient and the physician. Despite the recent treatment advances, we still have limited data on the safety of TKIs in pregnancy and its effect on fertility. However, there is a cause for concern and heightened awareness following the occurrence of a constellation of rare congenital malformations and spontaneous abortions in association with imatinib therapy. When a patient becomes pregnant whilst receiving TKI therapy, the difficulty lies in balancing the risk to the foetus of continuing therapy versus the risk to the patient of treatment interruption and potentially losing optimal disease response. All couples should be counselled on the risks associated with pregnancy whilst receiving TKI therapy. This is an essential aspect in patient care and frequently not emphasized enough by physicians. At the time of diagnosis, fertility preservation should be discussed with both male and female patients of childbearing potential. They should be made aware of fertility options which are available such as semen cryopreservation, ovarian or oocyte retrieval and storage and embryo cryopreservation in view of the potential detrimental effect of TKIs on fertility and gonadal function. The recommendation given to patients planning pregnancy differs according to their disease response to TKI therapy, which is the most important prognostic factor in CML.

Adolescent and Young Adult Oncology, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology

“…166 The safety and efficacy of hormonal agents and targeted therapies have not yet been evaluated in well-controlled studies including pregnant women. [165][166][167][180][181][182] Currently, the use of such agents in pregnant women is not recommended.…”

Chronic myeloid leukemia and pregnancy: patient and partner perspectives

“…While not known to be directly mutagenic, the TKIs used to treat CML -while emblematic of the burgeoning field of targeted therapy -are not specific for the mutant BCR-ABL kinase. Off-target inhibition of other tyrosine kinases may impact male and female fertility, spermatogenesis, embryonic implantation, and fetal development [6]. No prospective studies have been or will be completed to assess impact of TKIs on human fertility and/or confirm safety of TKI therapy on spermatogenesis or fetal development.…”

“…Recurrent skeletal malformations as well as abnormalities in the renal, respiratory, and gastrointestinal system have been recorded [10]. Case reports and case series describing pregnancy outcomes in women taking secondgeneration TKIs suggest similar risks [3,6,11,12].…”

“…If a decision to continue with a pregnancy is made, TKI cessation is recommended immediately. CML management while holding or deferring TKI therapy is individualized with options including observation, leukopheresis for management of cytoses, and interferon therapy as outlined in several recent expert reviews [6,11,12]. Interferon is pregnancy risk category C, but clinical experience suggests safety in the second and third trimester [13,14].…”

Chemotherapy during Pregnancy: Cases of Hodgkin's and Non-Hodgkin's Lymphoma, Chronic Myeloid Leukemia, Breast Cancer, Nasopharyngeal Cancer, and Choriocarcinoma

“…However, TKIs are contraindicated during pregnancy. Only few investigators have suggested TKI use despite the known teratogenic effects [17,18]. Other therapeutic approaches such as leukapheresis and interferon (IFN)-α can be considered during pregnancy.…”