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For Pregnant Women With Lymphoma, Standard Combination Chemotherapy Given After First Trimester Associated With Few Complications

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Key Points

  • When administered past the first trimester in pregnant women with lymphoma, standard non-antimetabolite combination chemotherapy was associated with few complications and expected maternal survival.
  • In mothers with non-Hodgkin lymphoma, radiotherapy predicted inferior progression-free survival and poor ECOG performance status, and increased lactate dehydrogenase predicted inferior overall survival.
  • In mothers with Hodgkin lymphoma, multiparous status predicted improved progression-free survival, and presence of B symptoms at diagnosis predicted inferior progression-free survival.

Lymphoma is the fourth most frequent cancer to occur during pregnancy. In a multicenter retrospective analysis reported in Journal of Clinical Oncology, Andrew M. Evens, DO, MSc, of Tufts University Medical School, and colleagues examined treatment, complications, and outcomes for Hodgkin lymphoma and non-Hodgkin lymphoma (NHL) occurring during pregnancy. The findings indicate that standard, non-antimetabolite, combination chemotherapy can be administered past the first trimester with few complications and expected maternal survival.

Study Details

The study included 90 patients from 11 academic centers who had a diagnosis of NHL (n = 50) or Hodgkin lymphoma (n = 40) during pregnancy over a 13-year period (1999-2011). Patients had a median age of 30 years (range 18-44 years) and median diagnosis occurred at 24 weeks gestation. Advanced stage disease was present in 52% of patients with NHL and 25% of those with Hodgkin lymphoma (P = .01). Of patients with stage I to II disease, 17% of patients with NHL and 30% of patients with Hodgkin lymphoma had B symptoms or bulky disease.

Treatment Details and Outcome

Among the 90 patients, pregnancy was terminated in 6 (7%) to permit immediate chemotherapy. Among the other 84 patients, 28 (33%) had therapy deferred to postpartum, including 32% with NHL and 35% with Hodgkin lymphoma; these patients were diagnosed with lymphoma at a median of 30 weeks gestation (range 12-38 weeks). The 56 patients (67%) who received antenatal treatment had lymphoma diagnosis at a median of 22 weeks (range 6-32 weeks; P < .001), with no difference in median time of diagnosis according to lymphoma type.

Antenatal treatment was started in patients at a median of 25 weeks, with 89% receiving combination chemotherapy, most commonly with standard regimens for the particular lymphoma subtypes. Treatment was started in the second trimester in 37 patients (66%).  The overall response rate for the 56 patients who received antenatal therapy was 82%, including complete response in 64%; overall response rate was 71% (complete response in 50%) in NHL patients and 96% (complete response in 83%) in Hodgkin lymphoma patients (P = .03 for overall response rate, P = .013 for complete response).

Complications

The most common complication was induction of labor, which occurred in 33% of patients. Perinatal events included premature rupture of membranes in 13% and preeclampsia in 7%. Delivery was via cesarean section in 33% of patients, with such delivery occurring in more NHL patients (44% vs 19%, P = .007). Among the 83 patients for whom timing of delivery was available, 44% had preterm deliveries with no difference based on NHL vs Hodgkin lymphoma (51% vs 36%, P = .19).

Fetal Outcomes

The median gestation at delivery was 37 weeks (range 31-40 weeks). Gestation went to full term in 47 (56%) of 84 patients, with no differences according to lymphoma type or receipt of antenatal therapy. One miscarriage occurred at 19 weeks gestation in a 34-year-old patient with double-hit NHL following one cycle of R-CHOP (rituximab [Rituxan] plus cyclophosphamide, doxorubicin, vincristine, and prednisone). The median birth weight was 2,668 g (range 1,005-3,628 g). Although there was no difference in birth weight according to receipt of antenatal chemotherapy vs deferred therapy (2,670 g vs 2,665 g, P = .74), there was a trend for infants to be small for gestational age if their mothers had received antenatal therapy (41% vs 9%, P = .09).

Of gestations for which information was available, 8 (11%) of 72 infants, all born to mothers with NHL, required admission to the neonatal intensive care unit (median stay 12 days, range 3-40 days), with no differences based on antenatal therapy vs deferred therapy. Microcephaly was reported in one infant following four antenatal cycles of CHOP for diffuse large B-cell lymphoma in the mother, who started treatment at 28 weeks gestation and delivered at 38 weeks. Grade 1 pelviectasis occurred in an infant whose mother received four antenatal cycles of R-CHOP for diffuse large B-cell lymphoma at 21 weeks gestation and delivered at 34 weeks due to pre-eclampsia. No other malformations were detected.

Maternal Outcomes

At a median follow-up of 41 months (range 6-147 months), 3-year progression-free survival and overall survival rates were 53% and 82% for NHL patients and 85% and 97% for Hodgkin lymphoma patients; rates were 55% and 79% for patients with diffuse large B-cell lymphoma and 37% and 90% for patients with T-cell NHL (P = .43 and P = .60, respectively). There were eight deaths related to NHL, including five due to diffuse large B-cell lymphoma, one due to peripheral T-cell lymphoma–not otherwise specified, one due to Burkitt’s lymphoma, and one due to double-hit NHL.

In patients with NHL, all of whom received radiotherapy during pregnancy, radiotherapy was the only predictor of inferior progression-free survival (hazard ratio [HR] = 5.19, P = .003) and Eastern Cooperative Oncology Group (ECOG) performance status of 2 to 4 (HR = 5.51, P = .001), and increased lactate dehydrogenase (HR = 9.93, P = .03) predicted inferior overall survival. For patients with diffuse large B-cell lymphoma, radiotherapy predicted inferior progression-free survival (HR = 7.72, P = .008), and poor ECOG performance status predicted worse overall survival (HR = 2.33, P = .04). For patients with Hodgkin lymphoma, multiparous status predicted improved progression-free survival (HR = 0.07, P = .01), presence of B symptoms at diagnosis predicted inferior progression-free survival (HR = 10.78, P = .04), and no variables were predictive of overall survival.

The researchers emphasized that all patients in the study were co-managed with high-risk maternal-fetal medical consultation, an approach that was associated with expected lymphoma-related outcomes and maternal and fetal complications consistent with that of a healthy population.

They concluded: “[W]e found that standard chemotherapy regimens for NHL and [Hodgkin lymphoma] (without antimetabolites) administered during the second and third trimester, including as early as 13 weeks gestation in some cases, was associated with minimal maternal complications or fetal detriment. In addition, patients with low-risk clinical scenarios (eg, indolent NHL, low tumor burden, and/or late gestational diagnosis) had therapy safely deferred to postpartum.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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