Antineoplastic
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
No reports describing the use of ofatumumab in human pregnancy have been located. In monkeys, the antibody caused fetal B-cell depletions, and decreased placental, spleen, and thymus weights at doses similar to those used in humans. The potential long-term effects of these toxic effects have not been studied in animals. However, refractory chronic lymphocytic leukemia is a serious disease and the maternal benefit appears to outweigh the risks to the fetus. If the antibody must be used in pregnancy, the woman should be informed of the absence of human pregnancy data and the potential fetal risks.
FETAL RISK SUMMARY
Ofatumumab is an IgG1k human monoclonal antibody. It is indicated for the treatment of chronic lymphocytic leukemia refractory to fludarabine and alemtuzumab. The mean half-life, between the 4th and 12th IV infusion doses was about 14 days (range 2.3–61.5 days). The antibody does not bind normal human tissues other than B lymphocytes (1). Data on metabolism have not been found.
Reproduction studies have been conducted in monkeys. Doses that were 0.7 and 3.5 times the recommended human dose (assumed to be based on body weight) were given weekly during organogenesis (gestation days 20–50). No maternal toxicity or teratogenicity was observed. However, both doses depleted circulating B cells in the dams. Ofatumumab crossed the placenta and fetuses, delivered at gestational day 100, had decreased mean peripheral B-cell counts (about 10% of control values), splenic B-cell counts (about 15%–20% of control values), spleen weights (15% for the low dose and 30% for the high dose, compared with control values), and thymus weight (15% compared with controls). In addition, there also was a 10% decrease in placental weights. The potential long-term effects of B-cell depletions or decreases in spleen and thymus weights have not been studied in animals (1).
Studies for carcinogenic or mutagenic potential or effects on fertility have not been conducted (1).
It is not known if ofatumumab crosses the human placenta. The molecular weight (about 149,000) is high, but immunoglobulin G crosses the placenta late in pregnancy (see Immune Globulin Intravenous). Placental transfer of IgG was a function of dose, as well as gestational age. Moreover, ofatumumab crossed to the fetus in monkeys and, because the placentas in monkeys are similar to those in humans, the antibody should be expected to cross to the human fetus.
BREASTFEEDING SUMMARY
No reports describing the use of ofatumumab during human lactation have been located. It is not known if the antibody is excreted into breast milk. The molecular weight (about 149,000) is high, but the terminal half-life is very long (about 14 days). Because immunoglobulins are excreted into milk, exposure of a nursing infant might occur. The effect of this exposure is unknown, but published data suggest that neonatal and infant consumption of breast milk does not result in substantial absorption of maternal antibodies into the circulation (1). Nevertheless, cytopenia, progressive multifocal leukoencephalopathy, and small intestine obstruction have been observed in human adults treated with ofatumumab and, if a woman chooses to nurse while receiving this agent, her infant should be monitored for these toxicities.
Reference
1.Product information. Arzerra. GlaxoSmithKline, 2009.