Common brand names

• Revlimid

How it is administered

Lenalidomide is available as oral capsules in various strengths (2.5 mg, 5 mg, 10 mg, 15 mg, 20 mg, and 25 mg). It is taken by mouth, usually once daily, at about the same time each day, with or without food. The capsules should be swallowed whole with water and should not be opened, broken, or chewed.

For marginal zone lymphoma (MZL), lenalidomide is typically used in combination with a rituximab product. The recommended starting dose is 20 mg once daily on Days 1 to 21 of repeated 28-day cycles, for up to 12 cycles. Dose adjustments may be necessary based on side effects or kidney function.

How it works

Lenalidomide is an immunomodulatory agent, meaning it helps regulate the immune system. It is a thalidomide analogue with antiangiogenic (prevents the growth of new blood vessels that tumors need to grow) and antineoplastic (prevents the development and spread of tumors) properties. Lenalidomide works by targeting a protein called cereblon, which is part of a complex that marks certain proteins for destruction. This leads to the breakdown of proteins that help cancer cells survive.

In marginal zone lymphoma and other blood cancers, lenalidomide inhibits the growth and survival of abnormal lymphocytes (a type of white blood cell). It also boosts the activity of immune cells, such as T cells and natural killer (NK) cells, helping the body attack cancer cells more effectively. When combined with rituximab, lenalidomide enhances antibody-dependent cell-mediated cytotoxicity (ADCC), making rituximab more effective at killing lymphoma cells. Additionally, lenalidomide reduces the production of inflammatory substances that can support tumor growth.

Who should take it

Lenalidomide is indicated for adults with previously treated marginal zone lymphoma (MZL), in combination with a rituximab product. It is also used for other blood cancers, such as multiple myeloma, mantle cell lymphoma, follicular lymphoma, and certain types of myelodysplastic syndromes.

For MZL, lenalidomide is considered when the disease has relapsed or progressed after prior therapies. It is typically used in patients who have already received at least one previous treatment. The combination with rituximab has been shown to improve outcomes in patients with relapsed or refractory MZL, including those with nodal, splenic, or extranodal (MALT) subtypes.

Who should not take it

Lenalidomide should NOT be taken by:

• Women who are pregnant, as it can cause severe birth defects or death to an unborn baby. Women of childbearing potential must use two forms of contraception and have regular pregnancy tests before, during, and after treatment.
• Anyone with a known severe hypersensitivity to lenalidomide (such as angioedema, Stevens-Johnson syndrome, or toxic epidermal necrolysis).

Caution is also advised in patients with:

• Severe kidney impairment (dose adjustments are needed)
• A history of serious blood clots, as lenalidomide increases the risk of venous and arterial thromboembolism
• Serious liver problems
• A history of severe skin reactions to thalidomide or lenalidomide

Lenalidomide is not recommended for patients with chronic lymphocytic leukemia (CLL) outside of clinical trials, due to increased risk of death.

Commonly used with

For marginal zone lymphoma, lenalidomide is most commonly used in combination with rituximab, a monoclonal antibody that targets B-cells. This combination has been shown to be more effective than rituximab alone in relapsed or refractory MZL.

Lenalidomide may also be used with dexamethasone for multiple myeloma, and with other supportive medications such as blood thinners (to reduce the risk of blood clots) and antibiotics (to prevent infections).

Commonly tested with

Lenalidomide has been tested in combination with:

• Rituximab (for marginal zone lymphoma and follicular lymphoma)
• Dexamethasone (for multiple myeloma)
• Other chemotherapy agents in various blood cancers

Clinical trials have compared lenalidomide/rituximab to rituximab alone, and have also explored its use with other immunomodulatory or targeted therapies. In MZL, the AUGMENT and MAGNIFY studies are key trials supporting its use with rituximab.