Key takeaways:

• Immune checkpoint inhibitors did not produce increased pregnancy, fetal and neonatal adverse events compared with other anticancer drugs.
• Anti-PD1, anti-CTLA4 combo resulted in overreporting of preterm birth.

Use of immune checkpoint inhibitors for pregnant women with cancer may be safer than previously thought, according to study results published in JAMA Network Open.

Patients treated with immune checkpoint inhibitors (ICIs) did not experience significantly more pregnancy-related, fetal or neonatal adverse events compared with those who received other anticancer therapies.

“It is the beginning of a journey to search for the best information available to help navigate difficult decisions ahead, especially when recommendations regarding life-saving cancer treatment can appear to be at odds with the needs of the pregnancy and growing fetus,” Alisa Kachikis, MD, MSc, assistant professor at University of Washington, and Linda O. Eckert, MD, adjunct professor at University of Washington, wrote in an accompanying editorial about the findings.

They said the study “offers some hope in an area where data are otherwise sparse.”

Background and methodology

Only 0.1% of pregnancies occur during active cancer treatments, with breast cancer, cervical cancer, Hodgkin disease, malignant melanoma and leukemia being the most common types, according to background information provided by Paul Gougis, MD, department of medical oncology at Pitié Salpêtrière Hospital, Paris, and colleagues.

However, managing these cancers can be difficult as clinicians must balance the health of the patient and the fetus.

ICIs have proven effective in cancer care and researchers expect them to be used more often in this population in the future.

“Currently, the use of ICIs during pregnancy is discouraged due to the absence of safety data obtained in the pregnancy setting,” Gougis and colleagues wrote. “Given the major benefits associated with ICIs, data from large-scale studies exploring the toxic effects of these agents during pregnancy are crucial.”

Researchers acquired study data from VigiBase, WHO’s pharmacovigilance database that has accumulated more than 30 million case reports from 130 countries since 1967.

They evaluated 45 different adverse events in reports of women with a pregnancy-related reaction and interaction with at least one anticancer drug.

The final analysis included 3,558 reports (48.1% from the U.S.; mean age, 28.7 years; 2.6% had ICIs exposure).

ICIs included FDA-approved PD1, PD-L1, CTLA4 and LAG3 inhibitors.

Reporting odds ratio (ROR) of women having any pregnancy-related, fetal and neonatal adverse outcomes while receiving ICIs compared with other anticancer drugs served as the study’s primary endpoint.

Results and next steps

The ICI group had a 41.8% report rate of pregnancy, fetal and neonatal adverse events compared with 57.1% in the other anticancer drug cohort (ROR = 0.54; 95% CI, 0.35-0.82).

No significant overreporting of adverse events occurred in the ICI group for any of the 45 outcomes evaluated.

In the evaluation of ICI treatments, overreporting of preterm birth did occur when women received a combination of anti-PD1 and anti-CTLA4 compared with other anticancer medications (80% vs. 23%; ROR = 13.87; 95% CI, 3.90-49.28).

However, anti-PD-L1 and anti-CTLA4 did not produce overreporting of preterm birth when used individually.

Researchers noted 3.3% of ICI reports had suspected immune-related complications.

“One mother developed a combination of antiphospholipid syndrome, pneumonitis and thyroiditis associated with spontaneous abortion,” they wrote. “One report mentioned fetal pneumonitis, possibly immune-related and leading to neonatal respiratory distress syndrome. One newborn experienced intrauterine growth restriction, preterm birth and transient congenital hypothyroidism.”

Study limitations included lack of various data points, including timing of exposure to medications and tumor characteristics.

“The risk-benefit evaluation for both the mother and the fetus or newborn should be discussed case by case considering the oncologic urgency,” researchers wrote.

Kachikis and Eckert stressed the need for more research.

“While this study is a step forward, more studies on cancer treatment in pregnancy and funding for reproductive health research are needed to mitigate the fraught nature of these difficult decisions,” they wrote.