Lenalidomide is an immunomodulatory imide drug (IMiD) and a potent derivative of thalidomide. It is a cornerstone therapy for multiple myeloma and specific myelodysplastic syndromes in India. It exhibits anti-angiogenic, anti-proliferative, and immunomodulatory effects, including T-cell and NK-cell co-stimulation and modulation of cytokine production. It is a Schedule X drug in India due to its teratogenic potential and is strictly regulated under a Risk Evaluation and Mitigation Strategy (REMS) program.
Adult: Multiple Myeloma: 25 mg orally once daily on Days 1-21 of repeated 28-day cycles, with dexamethasone. MDS (5q-): 10 mg orally once daily. Mantle Cell Lymphoma: 25 mg orally once daily on Days 1-21 of repeated 28-day cycles.
Note: Swallow capsule whole with water. Can be taken with or without food. Do not break, chew, or open capsules. If powder from a broken capsule contacts skin, wash area immediately with soap and water.
Lenalidomide's exact mechanism is multifactorial. Its primary target is the E3 ubiquitin ligase substrate receptor cereblon (CRBN). Binding to CRBN within the CRL4^CRBN E3 ubiquitin ligase complex alters its substrate specificity. This leads to the ubiquitination and subsequent proteasomal degradation of key lymphoid transcription factors Ikaros (IKZF1) and Aiolos (IKZF3). Depletion of these proteins results in: 1) Direct cytotoxic effects on malignant plasma cells (multiple myeloma) and del(5q) MDS cells, 2) Immunomodulation via T-cell and Natural Killer (NK)-cell activation, and 3) Inhibition of angiogenesis by reducing VEGF and bFGF secretion.
Pregnancy: CATEGORY X. Extremely high risk of severe life-threatening birth defects (limb abnormalities, cardiac defects, neural tube defects) and fetal death. Absolute contraindication. Women of childbearing potential must use TWO reliable forms of contraception 4 weeks before, during, and 4 weeks after therapy. Negative pregnancy tests required before, during, and after therapy.
Driving: May cause dizziness, fatigue, and somnolence. Patients should be cautioned about operating machinery or driving until they know how the drug affects them.
| Dexamethasone | Increased risk of venous thromboembolism (VTE) and toxicities like hyperglycemia. Requires VTE prophylaxis. | High |
| Erythropoiesis-Stimulating Agents (ESA) | Increased risk of thrombosis and reduced survival in MDS. Use with extreme caution. | High |
| Digoxin | Lenalidomide may increase digoxin serum levels. Monitor digoxin levels. | Moderate |
| Warfarin | Potential for altered INR. Monitor INR closely when starting or stopping lenalidomide. | Moderate |
| Live Vaccines | Risk of disseminated infection due to immunomodulatory effect. Contraindicated. | High |