Lenalidomide

IMiDs
Immunomodulatory imide drugs (IMiDs)
High alert
An error with this medicine can cause serious harm: double checks and protocols are used.
Pregnancy: contraindicated
Contraindicated: it is a thalidomide analogue and caused limb defects in animal studies. It is supplied only through a programme that requires pregnancy tests and effective…

Oral thalidomide derivative that makes cereblon destroy Ikaros and Aiolos. A myeloma mainstay; teratogenic, so it is dispensed under a restricted programme.

Updated Nov 1, 2026

Quick facts

Group: Immunomodulatory imide drugs (IMiDs)
Target: Cereblon (CRBN), substrate receptor of the CRL4 E3 ubiquitin ligase
Used for: Multiple myeloma · Transfusion-dependent anaemia
Key effects: Neutropenia and thrombocytopenia · Fatigue · Rash
Monitor: Pregnancy tests · Complete blood count regularly
ATC: L04AX04

No doses: the clinician sets them by the current guideline.

Mechanism of action

Cereblon (CRBN), substrate receptor of the CRL4 E3 ubiquitin ligaseLenalidomide

The crystal shows lenalidomide in the drug-binding pocket of human cereblon, bound to its partner protein DDB1.

Target in 3D: Cereblon (CRBN), substrate receptor of the CRL4 E3 ubiquitin ligase. PDB structure 4TZ4 (RCSB PDB, public domain). View the structure at RCSB PDB

Lenalidomide binds cereblon, part of a cullin-RING E3 ubiquitin ligase. The drug acts as a molecular glue: it changes cereblon's surface so the ligase grabs the transcription factors Ikaros and Aiolos (IKZF1 and IKZF3) and, in cells with deletion 5q, the kinase CK1α. These proteins are tagged with ubiquitin and destroyed by the proteasome. Myeloma cells, which depend on Ikaros and Aiolos, stop growing and die; T cells and natural killer cells become more active, and new blood vessel growth is reduced.

Lenalidomide binds the cereblon pocket
Cereblon now grabs Ikaros, Aiolos (and CK1α)
These proteins are ubiquitinated and destroyed
Myeloma cells die; T and NK cells are activated

Indications

Multiple myeloma: with dexamethasone, in combination regimens, and as maintenance after autologous stem cell transplant. Multiple myeloma →
Transfusion-dependent anaemia in lower-risk myelodysplastic syndrome with deletion 5q. Myelodysplastic syndromes →
Some B-cell lymphomas (mantle cell, follicular, marginal zone). Non-Hodgkin lymphoma →

Adverse effects

Common

Neutropenia and thrombocytopenia
Fatigue, diarrhoea or constipation, muscle cramps
Rash, itching
Upper respiratory infections

Contraindications

Pregnancy
Severe hypersensitivity (angioedema, anaphylaxis, severe skin reactions) to lenalidomide

Key interactions

Digoxin: Digoxin levels rise slightly: monitored periodically.
Erythropoiesis-stimulating agents and estrogen-containing therapies: Add to the risk of thrombosis.
Warfarin: Close INR monitoring in myeloma patients also taking dexamethasone.

What is monitored

Pregnancy tests in women who can become pregnant, before and during treatment, as the programme requires
Complete blood count regularly, more often at the start
Kidney function (dosing), liver tests and thyroid function
Signs of deep vein thrombosis or pulmonary embolism

Administration and safety

Dispensed only through a restricted programme with registered prescribers, pharmacies and patients.
Capsules are not opened, broken or chewed; powder on the skin is washed off with soap and water.
Thromboprophylaxis is chosen according to each patient's risk of clots.

Pregnancy and breastfeeding

Contraindicated: it is a thalidomide analogue and caused limb defects in animal studies. It is supplied only through a programme that requires pregnancy tests and effective contraception in women and condoms in men.

Nursing care

Confirm the pregnancy test and contraception requirements are met before each dispensing.
Teach the signs of a clot (leg swelling, chest pain, breathlessness) and of stroke, and to seek care at once.
Check counts and creatinine; report fever, bleeding or a new rash.
Teaching: no blood donation during treatment and for some weeks after; men use condoms even after vasectomy.

Pharmacokinetics

Absorption: Oral capsules, rapidly absorbed; can be taken with or without food.
Metabolism: Limited: it circulates mainly unchanged.
Elimination: Primarily by the kidneys, unchanged: the dose is adjusted in renal impairment.
Half-life: About 3 hours in healthy people and 3 to 5 hours in patients (label).

Test yourself

Think of the answer, then tap the question to see it.

What is the molecular target of lenalidomide?

Cereblon, the substrate receptor of the CRL4 E3 ubiquitin ligase.

Which proteins does lenalidomide mark for destruction in myeloma cells?

The transcription factors Ikaros (IKZF1) and Aiolos (IKZF3).

Which extra protein does lenalidomide send for destruction that matters in deletion 5q myelodysplastic syndrome?

The kinase CK1α.

Why must kidney function be checked before lenalidomide?

It is eliminated mainly unchanged by the kidneys; the dose is adjusted when kidney function is low.

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Connections

← Back to the class: Immunomodulatory imide drugs (IMiDs)

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: DailyMed - LENALIDOMIDE capsule (DailyMed (U.S. National Library of Medicine), 2026); Lenalidomide: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); RCSB PDB - 4TZ4: Crystal Structure of Human Cereblon in Complex with DDB1 and Lenalidomide (RCSB Protein Data Bank, 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.