Evaluation of the developmental toxicity of lenalidomide in rabbits

Christian, Mildred S.; Laskin, Oscar L.; Sharper, Valerie; Hoberman, Alan M.; Stirling, David I.; Latriano, Louise

doi:10.1002/bdrb.20115

Cited by 39 publications

(29 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lenalidomide has been reported previously to be nonteratogenic based on studies in rabbits (12). Our studies show a clear teratogenic effect of Lenalidomide on both chicken and zebrafish embryos at the concentration required to induce an antiinflammatory response.…”

Section: Discussionsupporting

confidence: 64%

“…However, long-term treatment with Lenalidomide can result in peripheral neuropathy (10,11) and, as yet, its teratogenic properties are uncertain, with only limited studies performed to date (12). Another Thalidomide analog, Pomalidomide, has shown promising treatment of relapsed and refractory multiple myeloma in phase I and phase II clinical trials, including in patients that have been treated previously with Thalidomide and Lenalidomide (13)(14)(15).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Pomalidomide is nonteratogenic in chicken and zebrafish embryos and nonneurotoxic in vitro

Mahony¹,

Erskine²,

Niven

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Thalidomide and its analog, Lenalidomide, are in current use clinically for treatment of multiple myeloma, complications of leprosy and cancers. An additional analog, Pomalidomide, has recently been licensed for treatment of multiple myeloma, and is purported to be clinically more potent than either Thalidomide or Lenalidomide. Using a combination of zebrafish and chicken embryos together with in vitro assays we have determined the relative anti-inflammatory activity of each compound. We demonstrate that in vivo embryonic assays Pomalidomide is a significantly more potent anti-inflammatory agent than either Thalidomide or Lenalidomide. We tested the effect of Pomalidomide and Lenalidomide on angiogenesis, teratogenesis, and neurite outgrowth, known detrimental effects of Thalidomide. We found that Pomalidomide, displays a high degree of cell specificity, and has no detectable teratogenic, antiangiogenic or neurotoxic effects at potent anti-inflammatory concentrations. This is in marked contrast to Thalidomide and Lenalidomide, which had detrimental effects on blood vessels, nerves, and embryonic development at anti-inflammatory concentrations. This work has implications for Pomalidomide as a treatment for conditions Thalidomide and Lenalidomide treat currently.

show abstract

Section: Discussionsupporting

confidence: 64%

mentioning

confidence: 99%

Pomalidomide is nonteratogenic in chicken and zebrafish embryos and nonneurotoxic in vitro

Mahony¹,

Erskine²,

Niven

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…It is uncommon for a test agent to induce these effects at nonmaternally toxic doses, that is, to be selective for the embryo. It is an unusual feature of thalidomide that it caused high incidences of unusual malformations at nonmaternally toxic doses in rabbits and primates (e.g., Christian et al, ). Artesunate, artemether, and DHA have also caused embryo deaths and/or malformations at nonmaternally toxic doses when tested in rats, rabbits, and/or monkeys (Clark et al, , , ).…”

Section: Developmental Toxicity Studies In Animals and Their Interprementioning

confidence: 99%

Animal Embryotoxicity Studies of Key Non‐Artemisinin Antimalarials and Use in Women in the First Trimester

Clark

2017

Birth Defects Research

View full text Add to dashboard Cite

The World Health Organization currently recommends quinine1clindamycin for use against malaria in the first trimester. This may soon change to recommending artemisinin-based combination therapies (standard duration of dosing 5 3 days). The non-artemisinin partner drugs include amodiaquine, lumefantrine, mefloquine, piperaquine, sulfadoxine1pyrimethamine, and pyronaridine. For quinine, clindamycin, and mefloquine and the combinations of sulfadoxine1pyrimethamine and artemether1lumefantrine, there are reports (including studies without internal comparison groups) that combined describe 304 to >1100 exposures of women in the first trimester for each drug with no conclusive evidence of adverse effects on pregnancy at therapeutic doses. This is despite the fact that all of these drugs or drug combinations caused embryo deaths and/or malformations in at least one animal species and all except lumefantrine had at least one exposure ratio <1. It now seems that these animal studies overestimated the risk of developmental toxicity in women with malaria. Three other non-artemisinins (amodiaquine, piperaquine, and pyronaridine) have few or no reported exposures in women in the first trimester and have exposure ratios 2 based on studies in pregnant rats and rabbits with dosing throughout organogenesis. However, none of these drugs caused embryo deaths or malformations in pregnant rats and rabbits with the exception of pyronaridine, which caused embryo deaths only at a dose that was excessively toxic to the mothers. Thus, for amodiaquine, piperaquine, and pyronaridine, the testing in animals did not reveal findings of concern and the exposure ratios were in the range of the other non-artemisinin antimalarials described above.

show abstract

“…A novel generation IMiD, slenalidomide, caused thalidomide-like fetal malformations in monkeys (71), but not in rabbits (72). Pomalidomide, another thalidomide analogue approved by the FDA, was teratogenic in both rats and rabbits when administered during the period of organogenesis (73).…”

Section: Adverse Effectsmentioning

confidence: 99%

Thalidomide and its analogues: A review of the potential for immunomodulation of fibrosis diseases and opthalmopathy (Review)

et al. 2017

View full text Add to dashboard Cite

Abstract. The US Food and Drug Administration approved thalidomide and its analogues for the treatment of erythema nodosum leprosum, in spite of the notoriety of reports of severe birth defects in the middle of the last century. As immunomodulatory drugs, thalidomide and its analogues have been used to effectively treat various diseases. In the present review, preclinical data about the effects of thalidomide and its analogues on the immune system are integrated, including the effects of cytokines on transdifferentiation, the anti-inflammatory effect, immune cell function regulation and angiogenesis. The present review also investigates the latest developments of thalidomide as a therapeutic option for the treatment of idiopathic pulmonary fibrosis, skin fibrosis, and ophthalmopathies.

show abstract

Evaluation of the developmental toxicity of lenalidomide in rabbits

Cited by 39 publications

References 46 publications

Pomalidomide is nonteratogenic in chicken and zebrafish embryos and nonneurotoxic in vitro

Pomalidomide is nonteratogenic in chicken and zebrafish embryos and nonneurotoxic in vitro

Animal Embryotoxicity Studies of Key Non‐Artemisinin Antimalarials and Use in Women in the First Trimester

Thalidomide and its analogues: A review of the potential for immunomodulation of fibrosis diseases and opthalmopathy (Review)

Contact Info

Product

Resources

About