Revlimid

Pronunciation

REV-lih-mid

Lenalidomide

Summary

• A drug that is similar to thalidomide, and is used to treat multiple myeloma and certain types of anemia.
• It is also used to treat mantle cell lymphoma that has come back or has not gotten better after other treatment.
• It is being studied in the treatment of other conditions and types of cancer.
• Revlimid may help the immune system kill abnormal blood cells or cancer cells.
• It may also prevent the growth of new blood vessels that tumors need to grow.
• It is a type of antiangiogenesis agent and a type of immunomodulating agent.
• Also called CC-5013 and lenalidomide.

FDA warning

• Lenalidomide, a thalidomide analogue, caused limb abnormalities in a developmental monkey study similar to birth defects caused by thalidomide in humans.
• If lenalidomide is used during pregnancy, it may cause birth defects or embryo-fetal death.
• Pregnancy must be excluded before start of treatment. Prevent pregnancy during treatment by the use of two reliable methods of contraception.
• Revlimid is available only through a restricted distribution program, called the Revlemid REMS® program

Indications

• Revlimid 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 follicular lymphoma (FL), in combination with a rituximab product.
• Previously treated marginal zone lymphoma (MZL), in combination with a rituximab product.

Lenalidomide ball-and-stick

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 actions

• 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.
• Lenalidomide inhibits proliferation and induces apoptosis of certain hematopoietic tumor cells including MM, mantle cell lymphoma, and del (5q) myelodysplastic syndromes, follicular lymphoma and marginal zone lymphoma
• in vitro Lenalidomide causes a delay in tumor growth in some

in vivo

• nonclinical hematopoietic tumor models including MM.
• Immunomodulatory properties of lenalidomide include increased number and activation of T cells and natural killer (NK) cells leading to direct and enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) via increased secretion of interleukin-2 and interferon-gamma, increased numbers of NKT cells, and inhibition of pro-inflammatory cytokines (e.g., TNF-α and IL-6) by monocytes.
• In MM cells, the combination of lenalidomide and dexamethasone synergizes the inhibition of cell proliferation and the induction of apoptosis. The combination of lenalidomide and rituximab increases ADCC and direct tumor apoptosis in follicular lymphoma cells and increases ADCC in marginal zone lymphoma cells compared to rituximab alone in vitro.

Limitations of Use

REVLIMID is not indicated and is not recommended for the treatment of patients with chronic lymphocytic leukemia (CLL) outside of controlled clinical trials.

Dosage

• Multiple myeloma combination therapy: 25 mg once daily orally on Days 1-21 of repeated 28-day cycles.
• Multiple myeloma maintenance therapy following auto-HSCT: 10 mg once daily continuously on Days 1-28 of repeated 28-day cycles.
• Myelodysplastic syndrome: 10 mg once daily.
• Mantle cell leukemia: 25 mg once daily orally on Days 1-21 of repeated 28-day cycles.
• Follicular lymphoma or marginal zone lymphoma: 20 mg once daily orally on Days 1-21 of repeated 28-day cycles for up to 12 cycles.
• Renal impairment: Adjust starting dose based on the creatinine clearance value.

Dosage forms

Capsules: 2.5 mg, 5 mg, 10 mg, 15 mg, 20 mg, and 25 mg.

Contraindications

• Pregnancy
• Demonstrated severe hypersensitivity to lenalidomide.

Side effects

Side effects vary based on the indication as noted below:

• Multiple myeloma: Most common adverse reactions (≥20%) include diarrhea, fatigue, anemia, constipation, neutropenia, leukopenia, peripheral edema, insomnia, muscle cramp/spasms, abdominal pain, back pain, nausea, asthenia, pyrexia, upper respiratory tract infection, bronchitis, nasopharyngitis, gastroenteritis, cough, rash, dyspnea, dizziness, decreased appetite, thrombocytopenia, and tremor.
• Myelodyspastic syndrome: Most common adverse reactions (>15%) include thrombocytopenia, neutropenia, diarrhea, pruritus, rash, fatigue, constipation, nausea, nasopharyngitis, arthralgia, pyrexia, back pain, peripheral edema, cough, dizziness, headache, muscle cramp, dyspnea, pharyngitis, [[and epistaxis.
• Non-Hodgkin's lymphoma (NHL: MCL, FL or MZL): Most common adverse reactions (≥15%) included neutropenia, thrombocytopenia, anemia, leukopenia, diarrhea, constipation, nausea, fatigue, pyrexia, cough, upper respiratory tract infection, and rash.

History

Lenalidomide was first approved for medical use in the United States in 2005 by the US FDA.

Cost

Lenalidomide costs US$163,381 per year for the average person in the United States as of 2012.

• Dailymed label info on Revlimid
• FDA Revlimid

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