Pharmacology Update

Lenalidomide Capsules (Revlimid®)

By William T. Elliott, MD, FACP, and James Chan, PhD, PharmD. Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Assistant Clinical Professor of Medicine, University of California, San Francisco; Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Chan and Elliott report no financial relationships to this field of study.

Lenalidomide, an analog of thalidomide has been approved for use in selected patients with transfusion dependant myelodysplastic syndrome. It possesses immunomodulating and antiangiogenic properties and is marketed by Celgene Corporation as Revlimid®. Due to potential toxicity, the product is available only to prescribers, pharmacists, and patients who are registered in the REVASSISTSM program.

Indications

Lenalidomide is indicated for the treatment of patients with transfusion-dependent anemia due to low or intermediate-risk myelodysplastic syndrome associated with a deletion 5q cytogenic abnormality with or without additional cytogenetic abnormalities.1

Dosage

The initial dose is 10 mg daily with water. The treatment should be interrupted if thrombocytopenia or neutropenia occurs and may be restarted at a lower dose (5 mg daily) if recovery to specified levels is achieved during the hiatus.1

Lenalidomide is supplied as 5 mg and 10 mg capsules.

Potential Advantages

Transfusion independence was achieved in 67% of patients treated with lenalidomide (99/148). The median transfusion-free period was 44 weeks.1

Potential Disadvantages

Adverse events are common; interruption or dose reduction was required in about 80% of patients in the clinical trial (n = 148). The median time to first dose reduction or interruption was 21 days and the duration of interruption was 22 days. About one third of patients required a second interruption or dose reduction.1

As an analog of thalidomide, lenalidomide has the potential to cause birth defects. Special prescribing requirements are in place to reduce this serious potential teratogenicity. Lenalidomide is associated with significant neutropenia, thrombocytopenia and increased risk of deep vein thrombosis and pulmonary embolism. Other adverse events include pruritus, rash, dry skin diarrhea, constipation, nausea, abdominal pain, vomiting, cough, nasopharyngitis, and dyspnea.1

Comments

Lenalidomide is an analog of thalidomide with greater potency, but with a better safety profile. It has shown activity in patients with myelodysplastic syndrome who have not responded to treatment with erythropoietin or who had high endogenous erythropoietin.2 Patients with a deletion 5q cytogenetic abnormality showed the highest response. The major drawback of lenalidomide is significant myelosuppression (Grade 3 or 4) necessitating dose reduction or therapy interruption in about 80% of patients. Other serious adverse events are potential for teratogenicity, deep vein thrombosis, and pulmonary embolism.1 Female patients with child bearing potential must use effective contraception for at least 4 weeks before beginning therapy, through any therapy interruption, and 4 weeks after discontinuation. Male patients should never have unprotected sexual contact with a female who can become pregnant. Lenalidomide is available only under a restricted distribution program, RevassistSM. The wholesale cost of lenalidomide is $6,450 for a 30-day supply.

Clinical Implications

Myelodysplastic syndromes are a group of bone marrow disorders characterized by ineffective production of normal mature red cells with a risk of progressing to leukemia.3 The 5q syndrome is the most distinct of the myelodysplastic syndromes.4 WHO defines this syndrome as having medullary and peripheral blast count of < 5%. Most patients require red blood cell transfusion sometime during their illness and some are transfusion dependent from the time of diagnosis.3 Approximately 40-60% of patients with low and intermediate risks are transfusion dependent.5 Frequent transfusions are often associated with clinical complications (eg, iron overload, transfusion reactions, infections) and reduced quality of life. Initial therapy generally involves hematopoietic growth factors. Patients with low-risk or intermediate-risk 5q abnormality may be considered candidates for lenalidomide.3 These patients have the best chance for survival (median, 3.5-5.7 years) and the longest time to the point when 25% of the group develop leukemia (3.3-9.4 years).

References

1. Revlimid Product Information. Celgene Corporation.

2. List A, et al. Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med. 2005;352:549-557.

3. Steensma DP, Bennett JM. The myelodysplastic syndromes: diagnosis and treatment. Mayo Clin Proc. 2006;81:104-130.

4. Giagounidis AAN, et al. The 5q- syndrome. Hematology. 2004;9:271-277.

5. Balducci L. Transfusion independence in patients with myelodysplastic syndromes: impact on outcomes and quality of life. Cancer. 2006;106:2087-2094.