Dallas, TX — The intersection of cancer diagnosis and pregnancy, or the occurrence of pregnancy during cancer treatment, remains uncommon. Oncology nurses are well-versed in the teratogenic effects of chemotherapy and fetal malformation risks. The approval of pembrolizumab (Keytruda) in 2014 marked a transformative shift in cancer therapy through immune checkpoint inhibitors (ICIs). However, caution is advised regarding the administration of ICIs during pregnancy. Oncology nurses play a pivotal role in educating patients on treatment protocols, potential side effects, fertility concerns, and the implications for pregnancy and the fetus.
ICIs are integral to treating various cancers and are commonly used among women of reproductive age. The potential adverse effects of ICIs on pregnancy necessitate a cautious approach. Both the American Society of Clinical Oncology (ASCO) and the European Society of Medical Oncology recommend avoiding ICIs during pregnancy, advocating for treatment postponement until after delivery. The FDA classifies anti-PD-1 immunotherapy (e.g., pembrolizumab) as category D, indicating evidence of fetal harm. CTLA-4-targeting medications (e.g., ipilimumab [Yervoy]) are categorized as category C, with animal studies suggesting potential harm to fetuses but insufficient human data. Close monitoring for pregnancy complications is recommended if ICIs are administered during pregnancy.
Pregnancy and cancer share similarities in immunological responses, utilizing similar immune checkpoint pathways to regulate immune function. During pregnancy, maternal immune systems undergo modifications to accommodate the fetus and prevent rejection, crucial for a successful pregnancy. Regulatory mechanisms that support immunological tolerance of the fetus are pivotal. Failure to activate these mechanisms may result in fetal malformation or miscarriage due to heightened immune responses.
Key checkpoint proteins involved in pregnancy’s immune-regulatory processes include PD-1, CTLA-4, and TIM-3. Elevated PD-1 expression during pregnancy, particularly within the PD-1/PD-L1 pathway, plays a crucial role in maintaining immune tolerance and shielding the fetus from maternal immune responses. Various immune cells, such as dendritic cells, regulatory T cells, and innate lymphoid cells, contribute to activating these regulatory mechanisms.
In cancer, PD-1/PD-L1 pathways are exploited by cancer cells to evade immune recognition. ICIs reactivate T cells and assist in identifying and attacking cancer cells. However, administering ICIs during pregnancy can disrupt PD-1 expression and the PD-1/PD-L1 pathway, potentially triggering immune responses against the fetus and leading to preterm labor.
Literature on ICIs during pregnancy remains contentious, primarily based on preclinical data. Reviews suggest pregnancy could elevate risks of complications such as miscarriage, premature birth, intrauterine growth retardation, HELLP syndrome, and low fetal heart rate. While cases of full-term deliveries of healthy infants have been reported, literature also documents instances of transplacental metastasis. Managing ICI-related adverse events during pregnancy could affect fetal development, glucose metabolism, and predispose to conditions like gestational diabetes and placental insufficiency.
Navigating pregnancy post-immunotherapy treatment requires a multidisciplinary approach, with guidelines recommending a delay ranging from six months to five years post-treatment completion. Personal factors like age, overall health, cancer type and stage, treatment response, and risk of recurrence are critical considerations. Emotional readiness and fear of cancer recurrence also influence decisions.
Oncology nurses are pivotal in informing patients about the implications of immunotherapy on fertility and pregnancy, emphasizing potential risks and benefits of treatment, closely monitoring side effects, and providing emotional support. Discussions on fertility preservation before treatment initiation, along with contraception options during treatment to prevent pregnancy, are essential.
ICIs have significantly improved cancer treatment outcomes and survival rates, particularly among women of childbearing age. Nonetheless, understanding their potential impacts on pregnancy and fetus is crucial, even as ethical constraints limit extensive research. Current evidence underscores the potential adverse effects of ICIs on pregnancy and emphasizes the importance of informed decision-making and comprehensive patient education.
