Immunotherapy During Pregnancy Just as Safe as Other Cancer Drugs

The use of immune checkpoint inhibitors (ICIs) during pregnancy was not associated with more adverse pregnancy, fetal, or newborn outcomes compared with other anticancer drugs, a cohort study showed.

Adverse pregnancy, fetal, or neonatal outcomes were reported in 41.8% of the 91 women exposed to ICIs during pregnancy compared with 57.1% of the 3,467 who were treated with non-ICI anticancer drugs (reporting odds ratio [ROR] 0.54, 95% CI 0.35-0.82), reported Paul Gougis, MD, of the Pitié Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, and colleagues.

While there have been concerns about pregnancy outcomes with maternal exposure to immunotherapy, "ICI use during pregnancy may be better tolerated than previously suspected," the authors concluded in JAMA Network Open.

However, of note, preterm birth was significantly over-reported among women treated with a combination of anti-PD-1 and anti-CTLA-4 therapies compared with other anticancer drugs (80% vs 23%; ROR 13.87, 95% CI 3.90-49.28, P<0.001), though this was not the case for anti-PD-L1 or anti-CTLA-4 monotherapy.

Gougis and team pointed out that this observation appears to support previous findings that the combination of anti-PD-1 and anti-CTLA-4 therapy is associated with higher toxicity compared with ICI monotherapy.

They also identified three reports of possible immune-related adverse events -- a case of maternal antiphospholipid syndrome leading to spontaneous abortion, a case of pneumonitis leading to neonatal respiratory distress syndrome and death, and a case of transient congenital hypothyroidism.

"These observations underscore the potential for rare but potentially severe immune-mediated maternofetal adverse events," they wrote, adding that "ICI use in pregnant women should be avoided when possible, especially the anti-PD-1 plus anti-CTLA-4 combination."

In an accompanying commentary, Alisa Kachikis, MD, and Linda O. Eckert, MD, both of the University of Washington in Seattle, noted that the combination of pregnancy and a cancer diagnosis often results in treatment recommendations that appear to conflict with the needs of the pregnancy and fetus.

Therefore, the study "offers some hope in an area where data are otherwise sparse," they wrote.

While the study is limited by its retrospective study design, small sample size, and a lack of detail on timing of exposure and specific adverse events, "in cases of rare diseases and/or rare therapies in pregnancy, benchmark study designs, such as randomized clinical trials, will likely never be feasible on a large scale," they added.

Furthermore, gathering information on uncommon complications associated with these therapies during pregnancy is difficult at best, they pointed out. "Unless use of ICIs in pregnancy becomes more common, there will likely always be limitations of available data in published literature regarding pregnancy, fetal and neonatal outcomes, and potential mitigation of treatment risks."

"Thankfully, cancer in pregnancy is rare and not all cancer treatment regimens place the health of the pregnant person and best chance at a favorable prognosis at odds with a successful pregnancy and healthy fetus," Kachikis and Eckert concluded. "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."

For this study, Gougis and colleagues assessed whether 45 distinct adverse pregnancy, fetal, or neonatal outcomes were associated with use of anticancer agents during pregnancy via VigiBase, the WHO's pharmacovigilance database containing over 30 million specific case safety reports from over 130 countries dating back to 1967.

The authors identified 3,558 reports for the final analysis, including the 91 involving ICI exposure and the 3,467 involving other anticancer drugs.

Among the group exposed to ICIs, mean age was 28.9 years, and 65.9% were from the U.S. Melanoma and lymphoma were the most frequently diagnosed cancers in the ICI group, while breast cancer and chronic myeloid leukemia were the most frequent types of cancer in the non-ICI group.

Among those in the ICI group, 63.7% were exposed to anti-PD-1 therapy, 16.5% to anti-PD-1 plus anti-CTLA-4 therapies, 14.3% to anti-CTLA-4 therapy, 4.4% to anti-PD-L1 therapy, and 1.1% to anti-PD-1 plus anti-LAG3 therapy. An ICI was used in combination with a non-ICI anticancer agent in 11% of women.

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