No reports describing the use of brentuximab in human pregnancy have been located. The animal data in the only species studied suggest risk. Moreover, the mechanism of action suggests that the drug can cause fetal harm. If the drug must be used in pregnancy, avoiding the 1st trimester should be considered. In addition, the patient should be informed of the potential risk to her fetus.
No reports describing the use of brentuximab during human lactation have been located. The molecular weight (about 153,000) and minimal metabolism suggest that exposure of a nursing infant will be limited, if it occurs at all. However, immune globulin is excreted into colostrum during the first few days after birth, and brentuximab is an IgG1 antibody-drug conjugate. Nevertheless, the amount of the drug in colostrum or breast milk should be low, and the potential for harm of a nursing infant appears to be low.
Brentuximab Vedotin (Adcetris)
Pregnancy Recommendation:No Human Data—Animal Data Suggest Moderate Risk
Breastfeeding Recommendation:No Human Data—Probably Compatible
Brentuximab is an IgG1 antibody specific for human CD30 combined with a microtubule disrupting agent (MMAE) and a protease-cleavable linker. It is given as an IV infusion every 3 weeks. Brentuximab is indicated for the treatment of patients with Hodgkin's lymphoma after failure of autologous stem cell transplant (ASCT) or after failure of at least two prior multiagent chemotherapy regimens in patients who are not ASCT candidates. It also is indicated for treatment of patients with systemic anaplastic large cell lymphoma after failure of at least one prior multiagent chemotherapy regimen. The antibody-drug conjugate undergoes minimal metabolism, and the terminal half-life is about 4-6 days (1).
Animal Data: Reproduction studies have been conducted in rats. During organogenesis, embryo-fetal toxicities were observed in rats given IV doses of brentuximab that resulted in systemic exposures that were approximately the same as the human exposure. The drug-induced toxicities were increased early resorption (≥99%), postimplantation loss (≥99%), decreased number of live fetuses, and external malformations (umbilical hernias and malrotated hind limbs (1).
Carcinogenicity studies with brentuximab have not been conducted. Consistent with its mechanism of action, MMAE was genotoxic in the rat bone marrow micronucleus study, but it was not mutagenic in two assays. Fertility studies have not been conducted. However, impairment of male reproductive function and fertility was observed in repeat-dose toxicity studies in rats (1).
Placental Transfer: It is not known if brentuximab crosses the human placenta. The molecular weight (about 153,000) and minimal metabolism suggest that exposure of the embryo-fetus will be limited. However, immune globulin crosses the placenta, especially late in gestation (see Immune Globulin Intravenous), and the animal data (see above) suggests that the agent crosses the placenta in rats.