How Does Chemotherapy During Pregnancy Affect Outcomes in Patients With Hodgkin Lymphoma?

In patients diagnosed with Hodgkin lymphoma (HL) during pregnancy, antenatal chemotherapy is associated with increased preterm contractions and lower birthweight for newborns, according to an analysis published in The Lancet Haematology. However, despite the increased risk of complications, there is no significant difference in survival between women who received antenatal chemotherapy and those who did not.

“Because of the trend of increased maternal age, over time more patients are being diagnosed with cancer during pregnancy,” lead authors Charlotte Maggen, MD, from Department of Obstetrics and Gynecology at University Hospitals Leuven in Belgium, and researchers, explained. The start of chemotherapy during pregnancy might endanger obstetric and neonatal outcomes, prompting some clinicians to recommend deferring treatment until after delivery to minimize fetal risks in women with early-stage HL, while others recommend immediate treatment in patients with symptomatic or advanced-stage disease.

In this retrospective cohort study, Dr. Maggen and researchers looked at oncologic and obstetric data from the International Network on Cancer, Infertility, and Pregnancy (INCIP) to assess obstetric outcomes, antenatal management, and maternal survival in 134 women diagnosed with HL between 1969 and 2018. Their outcomes (including birthweight, obstetric or neonatal complications, admission to a neonatal intensive care unit [NICU], and maternal survival) were compared with 211 nonpregnant, stage-matched, prognostic score–matched controls.

In the INCIP group, 72 patients (54%) began treatment with standard ABVD chemotherapy (doxorubicin, bleomycin, vinblastine, dacarbazine) during pregnancy, starting on January 1, 1997. Of the remaining patients, 56 (42%) did not receive ABVD during pregnancy, and 6 (4%) received only radiation therapy. Radiation therapy was typically used in the “prechemotherapy era” before 1995, the authors noted.

There was no significant difference between newborns who were exposed (n=69) or not exposed to chemotherapy (n=42) in terms of the incidence of:

  • being small for gestational age (22% vs. 16%, respectively; p=0.46)
  • admission to the NICU (29% vs. 29%; p=0.50)
  • major neonatal complications (7% vs. 5%; p=0.41)

Conversely, more neonates prenatally exposed to chemotherapy were in the lower birthweight percentiles (p=0.035).

Chemotherapy treatment during pregnancy appeared to have a more substantial effect on maternal outcomes. Women who received antenatal therapy, compared with those who did not, had a greater number of obstetric complications (p=0.005), including preterm contractions (12% vs. 7%) and preterm rupture of membranes (5% vs. 0%).

In the survival analyses, which included 77 pregnant women and 211 nonpregnant women with HL, outcomes were similar, regardless of disease stage. For example, in 62 pregnant women with early-stage HL, the rate of 5-year progression-free survival (PFS) was 82.6%, compared with 88.3% in 142 nonpregnant controls (hazard ratio [HR] = 1.80; 95% CI 0.84-3.87; p=0.130). Rates of 5-year overall survival (OS) were similar in this group, as well: 97.3% versus 98.4%, respectively (HR=1.63; 95% CI 0.35-7.65; p=0.534).

In the 15 pregnant women and 69 nonpregnant controls with advanced-stage disease, there also was no difference in 5-year PFS (90.9% vs. 74.0% [HR=0.36; 95% CI 0.04-2.90; p=0.334) or 5-year OS (100% vs. 96.2% [HR = not estimable; p=0.146]).

“Maternal outcome in this study supports previous suggestions that, in selected patients [such as those who are asymptomatic or diagnosed in the early third trimester of pregnancy], delivery can be expedited and therapy started postpartum, bridging with steroids or vinblastine if appropriate,” the researchers wrote. However, because the results demonstrate that the exposure to chemotherapy during pregnancy might affect fetal growth, “regular obstetric follow-up in this high-risk population is warranted.”

According to the researchers, the primary limitation of the study was its retrospective design, which may have resulted in missing data, under-reporting of complications, confounding by which patients were selected for treatment, and the lack of age-matching across cohorts. These findings also are generalizable only to patients with HL, and not to other hematologic or solid tumor malignancies. The researchers are conducting ongoing investigations into obstetric and maternal outcomes in women diagnosed with breast cancer during pregnancy.

Study authors report no relevant conflicts of interest.

Reference

Maggen C, Dierickx D, Lugtenburg P, et al. Obstetric and maternal outcomes in patients diagnosed with Hodgkin lymphoma during pregnancy: a multicentre, retrospective, cohort study. Lancet Haematol. 2019;6:e551-e561.

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