- Drug class: Immunomodulatory imide drug (IMiD), 3rd-generation (after thalidomide, lenalidomide).
- Mechanism of action:
- Binds to cereblon (CRBN), a substrate receptor of the E3 ubiquitin ligase complex.
- Leads to degradation of transcription factors Ikaros (IKZF1) and Aiolos (IKZF3).
- Results in anti-proliferative, pro-apoptotic, and immune-stimulatory effects.
- Indications (FDA/EMA approved):
- Relapsed/refractory multiple myeloma in patients who have received at least 2 prior therapies (including lenalidomide and a proteasome inhibitor).
- Used in combination with dexamethasone ± monoclonal antibodies (e.g., daratumumab, isatuximab, elotuzumab).
- Off-label: Kaposi’s sarcoma (HIV-positive & negative).
- Dosing:
- 4 mg orally once daily, days 1–21 of a 28-day cycle.
- Continue until disease progression or unacceptable toxicity.
- Dose adjustments: renal and hepatic impairment.
- Black Box Warnings:
- Embryo-fetal toxicity (teratogenic, like thalidomide).
- Venous and arterial thromboembolism (requires prophylaxis with aspirin or anticoagulation, depending on risk).
- Key adverse effects:
- Hematologic: Neutropenia (very common), anemia, thrombocytopenia.
- Infections: Bacterial, viral (esp. pneumonia).
- Thromboembolism: DVT/PE risk (esp. with dexamethasone).
- Fatigue, constipation/diarrhea, rash.
- Rare: hepatotoxicity, secondary malignancies.
- Drug interactions:
- Substrate of CYP1A2 and CYP3A4 (avoid strong inhibitors/inducers).
- Enhanced thrombosis risk with dexamethasone, doxorubicin, erythropoietin, estrogen therapy.
- Monitoring:
- CBC weekly for first 8 weeks, then monthly.
- Signs of thrombosis or infection.
- Liver function tests.
- Pregnancy testing (REMS program).
