pomalidomide

Pomalidomide is an oral immunomodulatory imide drug (IMiD) used in cancer therapy. It is an analog of thalidomide with antiangiogenic and immunomodulatory properties. In the United States, pomalidomide in combination with dexamethasone is approved for adult patients with multiple myeloma who have received at least two prior therapies.

Mechanism: Pomalidomide binds to cereblon, part of an E3 ubiquitin ligase complex, leading to degradation of transcription factors IKZF1 (Ikaros) and IKZF3 (Aiolos). This modulates immune cell activity and reduces tumor growth, while also inhibiting tumor vasculature. The net effect includes enhanced T-cell and natural killer cell activity against myeloma cells.

Administration and monitoring: given orally on a 28-day cycle, with dexamethasone, and dose adjustments for toxicity. Pomalidomide is subject to strict risk-management programs due to teratogenicity and embryofetal toxicity; female patients of reproductive potential must use effective contraception and participate in a required pregnancy prevention program. Concomitant anticoagulation or antiplatelet therapy may be used to mitigate thromboembolism risk; regular blood counts are required due to cytopenias.

Common adverse effects include cytopenias (neutropenia, anemia, thrombocytopenia), fatigue, nausea, edema, and rash. Infections and thromboembolic events are possible. The drug carries a boxed warning for teratogenicity; it is contraindicated in pregnancy. It has been studied in combination regimens for other hematologic malignancies, with varying regulatory statuses.

Development and status: Pomalidomide was developed as an IMiD by Celgene; it was approved by the U.S. FDA in 2013 for multiple myeloma after at least two prior therapies. Celgene was acquired by Bristol Myers Squibb in 2019, and pomalidomide therapies continue under the Pomalyst brand.