indication

For the treatment of patients with transfusion-dependent anemia due to low- or intermediate- risk myelodysplastic syndromes associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities.

pharmacology

Lenalidomide, a thalidomide analogue, is an immunomodulatory agent possessing immunomodulatory and antiangiogenic properties. Lenalidomide inhibits the secretion of pro-inflammatory cytokines and increases the secretion of anti-inflammatory cytokines from peripheral blood mononuclear cells. Lenalidomide inhibits cell proliferation with varying effectiveness (IC50s) in some but not all cell lines. Lenalidomide is effective in inhibiting growth of Namalwa cells (a human B cell lymphoma cell line with a deletion of one chromosome 5) but is much less effective in inhibiting growth of KG-1 cells (human myeloblastic cell line, also with a deletion of one chromosome 5) and other cell lines without chromosome 5 deletions.

mechanism of action

The mechanism of action of lenalidomide remains to be fully characterized, however it has been demonstrated that lenalidomide inhibits the expression of cyclooxygenase-2 (COX-2), but not COX-1, in vitro. In vivo it induces tumor cell apoptosis directly and indirectly by inhibition of bone marrow stromal cell support, by anti-angiogenic and anti-osteoclastogenic effects, and by immunomodulatory activity

toxicity

The most frequently reported adverse events were related to blood and lymphatic system disorders, skin and subcutaneous tissue disorders, gastrointestinal disorders, and general disorders and administrative site conditions.

biotransformation

The metabolic profile of lenalidomide in humans has not been studied. In healthy volunteers, approximately two-thirds of lenalidomide is eliminated unchanged through urinary excretion. The process exceeds the glomerular filtration rate and therefore is partially or entirely active.

absorption

Rapidly absorbed following oral administration, with maximum plasma concentrations occurring between 0.625 and 1.5 hours post-dose. Co-administration with food does not alter the extent of absorption (AUC) but does reduce the maximal plasma concentration (C_max) by 36%. The pharmacokinetic disposition of lenalidomide is linear.

half life

3 hours

route of elimination

In healthy volunteers, approximately two-thirds of lenalidomide is eliminated unchanged through urinary excretion.