Lenalidomide

What it is and how it works

Mechanism of Action Lenalidomide is an analogue of thalidomide with immunomodulatory, antiangiogenic, and antineoplastic properties. Cellular activities of lenalidomide are mediated through its target cereblon, a component of a cullin ring E3 ubiquitin ligase enzyme complex. In vitro , in the presence of drug, substrate proteins (including Aiolos, Ikaros, and CK1α) are targeted for ubiquitination and subsequent degradation leading to direct cytotoxic and immunomodulatory effects.

Indications

Lenalidomide is a thalidomide analogue indicated for the treatment of adult patients with: Multiple myeloma (MM), in combination with dexamethasone . MM, as maintenance following autologous hematopoietic stem cell transplantation (auto-HSCT) . Transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q abnormality with or without additional cytogenetic abnormalities . Mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib . Previously treated marginal zone lymphoma (MZL), in combination with a rituximab product . Previously treated follicular lymphoma (FL), in combination with a rituximab product . Limitations of Use: Lenalidomide capsules are not indicated and are not recommended for the treatment of patients with chronic lymphocytic leukemia (CLL) outside of controlled clinical trials . Multiple Myeloma Lenalidomide capsules in combination with dexamethasone are indicated for the treatment of adult patients with multiple myeloma (MM).

Dosage and administration (summary)

combination therapy: 25 mg once daily orally on Days 1 to 21 of repeated 28-day cycles. . MM maintenance therapy following auto-HSCT: 10 mg once daily continuously on Days 1 to 28 of repeated 28-day cycles . MDS: 10 mg once daily . MCL: 25 mg once daily orally on Days 1 to 21 of repeated 28-day cycles . FL or MZL: 20 mg once daily orally on Days 1 to 21 of repeated 28-day cycles for up to 12 cycles . Renal impairment: Adjust starting dose based on the creatinine clearance value . For concomitant therapy doses, see Full Prescribing Information ( 2.1 , 2.4 , 14.1 , 14.4 ).

Contraindications

Pregnancy ( Boxed Warning , 4.1 , 5.1 , 8.1 ). Demonstrated severe hypersensitivity to lenalidomide ( 4.2 , 5.9 , 5.15 ). Pregnancy Lenalidomide capsules can cause fetal harm when administered to a pregnant female. Limb abnormalities were seen in the offspring of monkeys that were dosed with lenalidomide during organogenesis. This effect was seen at all doses tested.

Warnings and precautions

Increased Mortality: serious and fatal cardiac adverse reactions occurred in patients with CLL treated with lenalidomide capsules . Second Primary Malignancies (SPM): Higher incidences of SPM were observed in controlled trials of patients with MM receiving lenalidomide capsules . Increased Mortality: Observed in patients with MM when pembrolizumab was added to dexamethasone and a thalidomide analogue . Hepatotoxicity: Hepatic failure including fatalities; monitor liver function. Stop lenalidomide capsules and evaluate if hepatotoxicity is suspected .

Pregnancy

Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in females exposed to lenalidomide capsules during pregnancy as well as female partners of male patients who are exposed to lenalidomide capsules. This registry is also used to understand the root cause for the pregnancy.

Storage and supply

How Supplied Lenalidomide capsules are available as follows: 2.5 mg – Each size 4 capsule with white cap and body printed with “NAT” on cap and “2.5mg” on body in black ink contains 2.5 mg of lenalidomide.

Source: Lenalidomide (Lenalidomide) — US FDA prescribing information, 2026-05-27, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.