Non-Hodgkin Lymphoma

Pregnancy-associated NHL refers to a group of lymphoproliferative diseases that range from indolent to aggressive, although most documented cases tend to be aggressive or highly aggressive lymphomas. Diffuse large B-cell lymphoma (DLBCL) is the type of NHL most commonly reported in both pregnant and nonpregnant patients in Western countries. Patients with pregnancy-associated NHL have been reported to be at increased risk for preeclampsia, cesarean section, preterm births, and postpartum blood transfusions.

Treatment decisions depend on the type of lymphoma and gestational age. For indolent lymphoma, a watchful waiting approach can be utilized in most cases, with any type of treatment delayed until delivery, and a short course of corticosteroids can be used as bridging therapy. For aggressive lymphoma, a regimen of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) can be safely initiated once the pregnancy moves past the first trimester.

However, if immediate treatment is needed within in the first trimester, especially during weeks 2 through 10, termination of the pregnancy is recommended as multidrug regimens are toxic to the fetus at that stage. Central nervous system prophylaxis with high-dose methotrexate may be administered to patients at high risk for central nervous system relapse, but methotrexate is contraindicated until week 20 of pregnancy, and overall, its use is not recommended at any time point during pregnancy.

Although rare in pregnancy, Burkitt lymphoma is a highly aggressive disease and necessitates immediate treatment with antimetabolites, regardless of gestational age. As high-dose methotrexate is included in most treatment regimens and known to be highly teratogenic, immediate termination of the pregnancy is recommended in combination with prompt initiation of intensive chemotherapy. There are very few reported cases of patients with Burkitt lymphoma who have been treated during pregnancy, so outcomes are difficult to gauge. In 1 instance, a patient received a 21-day regimen of R-CHOP and intrathecal methotrexate and dexamethasone. She responded well to therapy and the fetus showed no signs of toxicity. But in another report, cyclophosphamide, doxorubicin, ifosfamide, etoposide, and high-dose cytarabine (IVAC) was given, and a stillbirth occurred at 20 weeks.

Novel Treatment Agents

Novel agents are making inroads into a growing number of cancer types, including lymphomas. For example, the monoclonal antibody brentuximab vedotin (BV) is being used in treatment regimens for stage III and IV HL, but experimental models show that when administered during organogenesis, BV can  cause embryofetal lethality and teratogenicity. As a result, pregnant patients have been excluded from clinical trials, and no cases of BV exposure during pregnancy have been reported to date.

“As for novel agents, the inclusion of these therapies in treatment strategies, as well as deliberation on their safety in pregnancy, is still ongoing,” said Dr Gurevich-Shapiro. “The use of some agents, such as antiprogrammed death ligand 1 antibodies, is contraindicated during pregnancy, but other agents, such as some monoclonal antibodies, are considered safe and should be administered when indicated.”

She added that her group is currently compiling a review of the safety of novel agents in pregnancy. “We should strive to continue understanding the mechanisms of these treatments in the gestational period,” she said.

Finally, Dr Gurevich-Shapiro emphasized that her group would like to “encourage treating physicians to seek advice from centers specializing in hematologic malignancies in pregnancy, because new evidence is constantly coming to light.”

Reference

Gurevich-Shapiro A, Avivi I. Current treatment of lymphoma in pregnancy [published online May 20, 2019]. Expert Rev Hematol. doi:10.1080/17474086.2019.1615878

This article originally appeared on Hematology Advisor