Lenalidomide Reproductive Toxicity and Carcinogenicity
In embryonic fetus developmental toxicity test, lenalidomide was given orally to pregnant monkeys. Teratogenic effects were observed, including thalidomide-like extremities. Exposure to the dose at which this phenomenon occurs is 0.17 times as the exposure to 25 mg of the maximum recommended dose (MRHD). Lenalidomide was administered orally to pregnant rabbits at doses up to 20 mg/kg/day, and one abortion occurred in the 20 mg/kg/day group. Developmental toxicity at a dose of ≥10 mg/kg/day，it includes loss increase after implantation (early and late absorption and intrauterine death)and macroscopic appearance abnormalities. And it reduced fetal weight and increased incidence of soft tissue and skeletal variations. No adverse effects were seen at the 3 mg/kg dose. The exposure at this dose was 1.3 times as the exposure to MRHD. In another experiment, lenalidomide was given continuously from the embryonic organ formation to the lactation period in pregnant rats, and the certain degree of sexual maturation was delayed in the offspring. Like thalidomide, rats do not adequately explain the potential effect of lenalidomide on human embryonic development.
Since the intended use of lenalidomide is to treat advanced cancer, no carcinogenicity studies have been conducted. After a 26 weeks of repeated dose administration on rats (up to 300 mg/kg/day), no proliferative or proliferative lesions were observed in the necropsy during the administration or recovery period (4 weeks after the administration). After the 52-week repeated dosing on monkeys (up to 2 mg/kg/day), no carcinogenesis or precancerous changes were observed during the dosing period.