Revlimid (also called lenalidomide) is an oral cancer drug that is used for the treatment of multiple myeloma. It is part of a class of drugs called Immunomodulatory drugs or IMiDs^®. IMIDs work against cancer cells by impacting the functioning of the immune system.

Revlimid is chemically related to Thalidomide, another IMID, but has been found to be more potent in the laboratory and has different side effects. For example, significant sleepiness, constipation and painful nerve problems (neuropathy), common side effects of Thalidomide, are seen much less frequently with Revlimid.

In addition to multiple myeloma, Revlimid is also used to treat another disease (myelodysplastic syndrome or MDS).

Revlimid is made by the Celgene Corporation.

Revlimid is a commonly used drug in all stages of multiple myeloma.

Although it can be used alone, it is usually used in combination with another anti-myeloma drug, dexamethasone (dex). This combination is called Revlimid-dex. The combination of Revlimid plus dexamethasone has been shown to be more effective than either drug taken alone.

Revlimid-dex is approved by the FDA for the treatment of multiple myeloma patients who have received at least one prior therapy. It is also commonly used for newly diagnosed or untreated patients.

Revlimid is now being studied for use as maintenance therapy following high-dose chemotherapy and stem cell transplant. Maintenance therapy is treatment that is given to patients in remission in order to reduce the risk of relapse.

In addition, Revlimid is also being studied in combination with other myeloma drugs (eg, Velcade) as well as other new drugs in development.

Revlimid works in multiple ways to slow or kill myeloma cells, although the exact way in which it works is not completely understood. It directly affects the tumor cells. It is also known to affect the blood vessels and other substances surrounding a tumor (known as the tumor microenvironment) which help to feed the cancer cell's growth.

Revlimid is a capsule that is taken every day for 3 weeks with a 1 week rest period. It is available in several strengths (5mg, 10mg, 15mg and 25mg capsules). The typical starting dose is 25 mg once a day. The minimum dose is 5 mg daily.

Dexamethasone is a pill that is taken along with Revlimid. The dose of dexamethasone is usually 40mg and may be given in two different ways — on a high-dose schedule or on a low-dose schedule.

High-dose dexamethasone is typically taken only on certain days of the month, at a starting dose of 40mg (usually given as ten 40mg strength pills). For the first four months, it is taken on days 1-4, 9-12 and 17-20 of each month. Starting at month 5, dexamethasone is only taken on days 1-4 of each month. Each month or 28-days of therapy is known a treatment cycle (usually called a 28-day treatment cycle). LEARN MORE »

Low-dose dexamethasone is given once a week. The starting dose of dexamethasone is 40 mg. LEARN MORE »

It is important to take Revlimid-dex exactly as your doctor has prescribed. If you miss or forget to take a dose, do not double the dose the next day. Re-start your therapy at your regular dose.

In addition, a blood thinner such as aspirin is typically taken along with Revlimid-dex to reduce the chance of developing a blood clot.

Your dose may be changed depending upon your response to therapy and side effects.

The length of treatment with Revlimid-dex is determined on an individual basis and may depend on a number of factors including:

• Response to therapy
• Side effects
• Whether the treatment plan includes high-dose chemotherapy and stem cell transplant (following Revlimid-dex)
• Patient preference

Patients who expect to proceed to high-dose chemotherapy and stem cell transplant may only receive a few cycles of Revlimid-dex, until they achieve a response. Other patients may choose to continue Revlimid-dex indefinitely, as long as the treatment is working and side effects are manageable. You and your doctor will discuss the length of treatment that is right for you.

It is important to remember that side effects of all treatments are based on the individual and vary from patient to patient. Most side effects of Revlimid-dex can be easily managed.

The most common side effects of Revlimid-dex seen in large clinical studies are:

• Low blood counts (also one of the most serious side effects)
• Constipation
• Muscle cramps
• Diarrhea (see more details below)
• Fatigue
• Insomnia

Update from recent studies: Increased diarrhea in patients taking Revlimid-dex for an extended period of time (>8 months)

• In studies with more than 700 patients, patients taking Revlimid-dex for more than 8 months experienced significantly more diarrhea than patients taking dex alone (39% vs 28% with dex alone).
• In the majority of patients, diarrhea started after taking Revlimid-dex for 19 months.
• In most cases, the diarrhea was mild or moderate and could be managed with Imodium^® (loperamide, Mc-Neil-PPC, Inc). However, the dose of Revlimid needed to be reduced for some patients.

The most serious side effects that may occur while taking Revlimid-dex are low blood counts, blood clots, rare rash or skin reactions and possible birth defects.

• Low blood counts: Two types of blood cells may be reduced while taking Revlimid:
  • Platelets: substances in the blood responsible for clotting. (low levels of platelets are also known as thrombocytopenia).
  • Neutrophils: a type of white blood cell that plays an important role in the immune system (low levels of neutrophils are called neutropenia).

Your doctor will monitor your blood counts. Typically, blood counts will be checked every 2 weeks for the first 12 weeks of therapy and at least monthly thereafter.

If your blood counts drop significantly, your doctor may temporarily stop or reduce your dose of Revlimid. If your counts are very low, your doctor may add another drug to help increase your blood counts (eg, colony-stimulating factor known as G-CSF).

• Serious blood clots in the veins or lungs (deep vein thrombosis, DVT or pulmonary embolism): These types of blood clots are potentially life-threatening. However, the risk of blood clots is decreased when patients take blood thinners along with their Revlimid-dex therapy.

• Very serious rash or skin reaction (Stevens-Johnson syndrome and toxic epidermal necrolysis): A few cases of very serious skin reactions or rashes have been seen in patients taking Revlimid. In these types of skin reactions, blisters may appear on a large percentage of the body.

Although, it is not clear whether or not Revlimid actually causes these problems, it is important to be aware of them because they can be life-threatening. Call your doctor immediately if you notice any type of unusual rash or skin reaction.

Possible birth defects: Although, Revlimid does not appear to cause the type of severe birth defects seen in the past with Thalidomide. Women who are pregnant or who plan to become pregnant must not take Revlimid. This precaution is due to its similarity to Thalidomide, and some signs of birth defects in animals. A program called RevAssist(SM)has been created to prevent exposure to Revlimid during pregnancy.

• Doctors and pharmacists must register with RevAssist in order to prescribe and dispense Revlimid.
• Patients must register and meet all the conditions of the program in order to take Revlimid.

In addition, dexamethasone by itself can cause side effects. Possible side effects of dexamethasone alone include: stomach problems, vomiting, headache, dizziness, insomnia, restlessness, depression, anxiety, acne, increased hair growth, and easy bruising.

Please tell your doctor or nurse if you experience any side effects.

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Management of side effects depends on the type and severity of the problem. Some side effects such as mild or moderate diarrhea can be managed with additional medications.

More serious side effects may require you to stop Revlimid-dex either temporarily or permanently. In many cases, Revlimid-dex is stopped temporarily, until the side effect improves, and then re-started at a lower dose. Studies have shown that Revlimid-dex is still effective at lower doses. LEARN MORE »

Although Revlimid in combination with dexamethasone has been FDA approved in myeloma only for patients who have received at least one prior therapy, this drug has also been shown to be effective in a wide range of patients including:

• Newly diagnosed/untreated myeloma and relapsed or refractory myeloma
• Older patients (≥65 years old) as well as younger patients
• Patients whose disease has certain high-risk features such as
  chromosome 13, chromosome 14 or 17 deletions or with an elevated β2-microglobulin level .
• Patients who previously received Thalidomide (although efficacy is slightly reduced)
• Patients who have received several prior therapies (heavily-pretreated)
  • One study showed that some of these patients responded for a long period of time (4 or more years)
• Patients who previously received high dose chemotherapy and stem-cell transplant
• Patients with reduced kidney function (renal impairment)
  • In one study, 78% of patients with moderate to severe renal impairment showed improved renal function within 4 months of treatment.

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Two large clinical studies have shown that Revlimid-dex significantly improves survival in patients with newly diagnosed/untreated myeloma.

• One study showed that Revlimid plus high-dose dex was more effective than high-dose dex alone. However, there were more side effects with Revlimid high-dose dex. LEARN MORE »

• Another important study showed that patients taking Revlimid plus low-dose dex had significantly improved survival and fewer side effects than patients taking Revlimid plus high dose dex.
  • One year after the beginning of treatment, 96% of patients taking Revlimid low-dose dex were alive and 88% were alive 2 years later.
    • There was no difference in survival time between patients who went on to high dose chemotherapy plus stem cell transplant and those who took Revlimid plus low-dose dex for an extended period of time (more than 4 months).
  • The incidence of serious (grade ¾) side effects was much lower with Revlimid plus low-dose dex versus Revlimid plus high-dose dex (30% versus 50%).
  LEARN MORE »

Based on these two studies, the combination of Revlimid-dex has become a commonly used option for newly-diagnosed/untreated patients. Many doctors recommend the combination of Revlimid and low-dose dex, particularly in patients over 65.

Large national studies (Phase III) are evaluating the efficacy and safety of combinations of Revlimid with other myeloma drugs.

• Revlimid in combination with Velcade and dexamethasone (also known as REV-VEL) is being compared to Velcade and dexamethasone in 440 patients eligible for high-dose chemotherapy and stem cell transplant.
  • Data from a small early study indicated that this combination may be very effective and with manageable side effects. 98% of patients responded to this treatment with 30% achieving a complete response. This response rate is one of the highest seen in newly diagnosed patients.
• Revlimid in combination with melphalan and prednisone (MP-R or R-MP) is being studied in patients over 65 years old (who are typically NOT eligible for high-dose chemotherapy and stem cell transplant).
  • The goal of these studies is to improve on an older treatment--the combination of melphalan and prednisone (also know as MP). Two large studies are underway. One study with 450 patients will compare MP-R to MP. Another study with 450 patients will compare MP-R to MP plus Thalidomide (also known as MP-T).
  • Researchers believe that Revlimid plus MP may be effective because the combination of MP and Thalidomide, a drug that is chemically similar to Revlimid, has been proven to be very effective.
  • In addition, promising results have been seen with MP-R in some small studies in relapsed and refractory patients. In one recent study, 69% of patients responded and 31% had a substantial reduction in M-protein (CR or VGPR).

In addition, several other combination treatments are being studied including:

• Revlimid, Velcade, dex, plus Cytoxan (a chemotherapy drug used for many cancers)
• Revlimid-dex plus Clarithromycin (Biaxin^™), an antibiotic. This combination is known as BiRD (Biaxin, in addition to Revlimid-dex).

Several studies are evaluating the use of Revlimid as a treatment following remission with the goal of reducing the risk of relapse. In particular, one large national study is evaluating Revlimid as maintenance therapy following high-dose chemotherapy and stem cell transplant.

A large national clinical trial is studying the effectiveness of Revlimid compared to observation in high risk asymptomatic patients. Typically, these patients are not given any myeloma treatment.

Visit the MMRF's Clinical Trials Matching Service to view a list of ongoing Revlimid clinical trials.

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Two large clinical trials showed that Revlimid-dex is significantly more effective than high-dose dexamethasone, a standard myeloma treatment in treating relapsed or refractory myeloma. Over 700 patients throughout the world participated in these studies.

Revlimid-dex significantly delayed disease progression and extended survival. Response rates were superior with Revlimid-dex as well

• Patients receiving Revlimid-dex lived nearly 3 years.
  • Those who received Revlimid-dex right after initial remission lived longer than those who received Revlimid-dex after 2 or more therapies
• Overall responses were nearly 3 times dex, with a high rate of complete responses
• Patients who had a partial response (PR), complete or near complete response (CR/nCR) generally started to respond 10-11 weeks after beginning treatment. These patients continued to respond for a much longer period of time than other patients. LEARN MORE »

These results were confirmed by another large study that enrolled 1400 patients in more than 100 sites throughout the US.

Although efficacy is higher in combination with another drug (eg, dex), Revlimid alone is still effective. It also has fewer side effects.

In one study with 200 patients, there were many patients who survived approximately 2 years after starting therapy with Revlimid alone. In addition, approximately one-third of patients responded to treatment, with the average responses lasting about one year. Even patients who relapsed after high-dose chemotherapy and stem cell transplant, benefited from treatment with Revlimid alone.

Revlimid alone may be appropriate for patients who are very frail or have a type of myeloma that tends to be very stable or slow growing (indolent disease).

Revlimid and Velcade^® (bortezomib) with or without dexamethasone (also known as VRD) appears to be one of the most promising new combinations. It is being studied in both relapsed/refractory myeloma and in newly diagnosed patients. VRD appeared to be very effective in a small study with patients who had received several prior therapies.

• 86% of patients responded to this treatment, with 24% of patients achieving a complete or near complete response.
• Patients with high-risk myeloma had similar outcomes as compared to other patients

Other promising new cancer drugs that are being studied in combination with Revlimid are listed below.

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