Revlimid®

What is Revlimid?

Revlimid, also known as 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 (IMiDs), which work against cancer cells partly by supporting the function of the immune system. Revlimid is manufactured by Celgene.

Revlimid is chemically related to Thalomid (thalidomide, Celgene), 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–which are common side effects of Thalomid—are seen much less frequently with Revlimid.

In addition to multiple myeloma, Revlimid is also used to treat other diseases (myelodysplastic syndrome and mantle cell lymphoma).


How is Revlimid used in multiple myeloma?

Revlimid is used throughout all stages of multiple myeloma.

The combination of Revlimid and dexamethasone, also called Revlimid-dex or Rd, is approved for the treatment of patients with multiple myeloma. This combination has been shown to be effective in both newly diagnosed myeloma and in disease that has relapsed or become refractory to current therapies. This combination, which can be used in all stages of myeloma, also serves as a backbone on which to add additional agents. Recent clinical trials have shown that adding a third agent to Rd improves patient outcomes even more than treatment with Rd alone.

Some of the Rd-based combination regimens are described below (you can find additional information on the applicable drug pages, accessible through the links provided):

  • Velcade (bortezomib, Takeda Oncology) (VRd regimen)
    • According to treatment guidelines, VRd is one of the preferred options for initial therapy of myeloma patients, regardless of whether they are transplant candidates.
    • VRd is highly effective against relapsed or refractory myeloma and is listed in current treatment guidelines as a preferred treatment option for treatment of patients with relapsed or refractory myeloma.
  • Kyprolis (carfilzomib, Amgen) (KRd regimen)
    • The phase 3 ASPIRE trial of patients with relapsed myeloma found that patients receiving KRd lived longer without their disease worsening than patients receiving Rd alone.
  • Ninlaro (ixazomib, Takeda Oncology) (IRd regimen)
    • The phase 3 TOURMALINE-MM1 trial of patients with relapsed or refractory multiple myeloma found that, on average, patients receiving IRd lived significantly longer without their disease worsening than patients receiving Rd (20.6 months vs 14.7 months).
  • Empliciti (elotuzumab, Bristol-Myers Squibb) (ERd regimen)
    • The phase 3 ELOQUENT-2 trial, which studied myeloma patients who had received one to three prior therapies and progressed following their most recent therapy, found that the addition of Empliciti to Rd resulted in a 30% reduction in risk of disease progression or death compared to Rd alone.
  • Darzalex (daratumumab, Janssen Biotech) (DRd regimen)
    • The phase 3 POLLUX trial of patients with multiple myeloma who had received at least one prior therapy found that patients receiving DRd had a 63% reduction in the risk of death.

Revlimid is also indicated for use as maintenance therapy following high-dose chemotherapy and autologous stem cell transplantation (ASCT).

What types of patients can benefit from Revlimid?

Revlimid has been shown to be effective in a wide range of patients including:

  • Those with newly diagnosed/untreated myeloma and relapsed or refractory myeloma
  • Older patients (over 65 years old) as well as younger patients
  • Patients whose disease has certain high-risk features
  • Patients who previously received Thalomid (though efficacy is slightly reduced)
  • Patients who have received several prior therapies (heavily pretreated)
    • One study showed that some of these patients had a lengthy response (4 or more years)
  • Patients who previously received high-dose chemotherapy and ASCT
  • 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.

How does Revlimid work?

Revlimid works in multiple ways to slow or kill myeloma cells, though the exact ways in which it works are 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) that help to feed the cancer cell’s growth. It has been shown in studies supported by the Multiple Myeloma Research Consortium (MMRC) that Revlimid and other IMiDs bind a protein in myeloma cells called cereblon. This binding triggers myeloma cell death. In some studies, higher levels of cereblon are associated with better outcomes after treatment.


How long is Revlimid administered?

Revlimid is administered orally.  Dosing varies depending on whether Revlimid is given in combination with other agents or as maintenance therapy following ASCT.

Revlimid Combination Therapy

Revlimid may be taken along with 40 mg dexamethasone. In this combination, Revlimid is administered at a starting dose of 25 mg once daily on days 1–21 for each 28-day cycle. The dose of dexamethasone is usually 40 mg and is given on days 1, 8, 15, and 22 of each 28-day cycle. For patients over 75 years of age, the starting dose of dexamethasone is 20 mg.

Revlimid Maintenance Therapy Following Autologous Stem Cell Transplant

Following ASCT, the starting dose of Revlimid is 10 mg once daily for days 1–28 of repeated 28-day cycles, until disease progresses or until the patient experiences unacceptable toxicity. The dose may be increased to 15 mg once daily if the 10-mg dose was well-tolerated for the first three cycles.

Patients who expect to proceed to high-dose chemotherapy and ASCT may only receive a few cycles of Rd, until they achieve a response. In this case, patients will also have their stem cells collected (harvested) within the first four cycles of treatment. Other patients may continue to receive Rd 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.


What are Revlimid side effects?

The most common side effects of Rd seen in patients with multiple myeloma in large clinical studies include:

  • Gastrointestinal effects (diarrhea, abdominal pain)
  • Fatigue, weakness, decrease appetite
  • Low red blood cell or white blood cell counts
  • Shortness of breath
  • Cough
  • Insomnia
  • Muscle spasms
  • Back pain
  • Fever
  • Rash

The most common side effects of Revlimid maintenance therapy following ASCT seen in patients with multiple myeloma in large clinical studies include:

  • Low red blood cell, white blood cell, or platelet counts
  • Upper respiratory infection, bronchitis, cold, or cough
  • Stomach flu
  • Diarrhea
  • Fatigue or weakness
  • Fever
  • Rash
  • Muscle spasms

The most common severe side effects of Rd include:

  • Low white blood cell, red blood cell, or platelet counts
  • Shortness of breath
  • Low potassium levels
  • Low blood sugar
  • Rash
  • Cataract
  • Renal failure
  • Fatigue or weakness
  • Back pain
  • Pneumonia
  • Blood clots

The most common severe side effects of Revlimid maintenance therapy include:

  • Low white blood cell, red blood cell, or platelet counts
  • Fever or infection due to low white blood cell count
  • Pneumonia or lung infection
  • Diarrhea or nausea
  • Fatigue
  • Low potassium levels
  • Low phosphate levels

Due to the possibility of low cell counts, patients taking Revlimid will have their blood checked weekly during the first two cycles, every other week during the third cycle, and monthly thereafter.

Because Revlimid can increase the risk of blood clots in the legs and lungs, patients taking Revlimid also receive a blood thinner (anticoagulant) such as aspirin or heparin. The choice of agent will be tailored to the patient based on his or her individual risk factors.

Other serious side effects that have been seen with Revlimid include heart attack and stroke, liver failure, and allergic reactions, including severe skin reactions.

Women who are pregnant or who plan to become pregnant must not take Revlimid because it may cause birth defects. A program called Revlimid Risk Evaluation and Mitigation Strategies (REMS) has been created to prevent exposure to Revlimid during pregnancy. Patients must register and meet all the conditions of the program in order to take Revlimid.

How are side effects of Revlimid managed?

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 either temporarily or permanently. In many cases, Revlimid is stopped temporarily, until the side effect improves, and then re-started at a lower dose. Studies have shown that Rd is still effective at lower doses.

Does Revlimid cause second cancers?

There have been reports of new second cancers (also called second primary malignancies or SPMs) developing in a small number of myeloma patients who received Revlimid therapy in clinical studies. In all of these studies Revlimid was used in combination with melphalan chemotherapy. The types of secondary cancers seen include myelodysplastic syndrome (a form of preleukemia) and acute myelogenous leukemia. There have been very few additional second cancers in other studies with Revlimid where melphalan was not part of the treatment. Overall, the information available to date indicates that therapy with Revlimid significantly decreases the risk of myeloma disease progression. Hence, some doctors believe that the benefits of Revlimid therapy may outweigh any potential risk of second cancers.


 

What have Revlimid clinical studies shown?

Revlimid clinical studies have shown improved survival in patients with newly diagnosed/untreated myeloma, in patients following ASCT, and in those who have had at least one prior therapy.

Revlimid in combination with dexamethasone in patients with newly diagnosed multiple myeloma (continuous Rd).

In a study of  newly diagnosed patients comparing Revlimid and low-dose dexamethasone (Rd) as a continuous dose until disease progression to melphalan, prednisone, and thalidomide (MPT), the time to disease progression was significantly longer for continuous Rd than for MPT. On average, the time that patients receiving Rd continuous lived without their disease worsening was 25.5 months compared with 21.2 months with MPT. Patients treated with Rd had an improvement in overall survival compared to those treated with MPT.

Revlimid as maintenance therapy in patients with newly diagnosed multiple myeloma following ASCT.

In two studies of patients taking Revlimid as maintenance therapy after ASCT, the time to disease progression was significantly longer for patients taking Revlimid than those receiving no maintenance. On average, the time that patients receiving Revlimid lived without their disease worsening was 33.9–41.2 months, compared with 19.0–23.0 months. In one study, patients treated with Revlimid had a 41% improvement in overall survival compared to those treated with placebo, while in the second study, no improvement in overall survival was observed.

There was a small increase in second new cancers in these studies, which did not affect the overall benefit of Revlimid on disease progression. Thus, some researchers believe that the benefits of maintenance therapy with Revlimid may outweigh the risks of a second new cancer.

Patients who have undergone a stem cell transplant should discuss with their doctors the pros and cons of maintenance therapy with Revlimid.

Revlimid plus high-dose dexamethasone for patients with multiple myeloma who relapsed after at least one prior therapy.

In two studies of patients with multiple myeloma who had received at least one prior treatment and were treated with Revlimid plus high-dose dexamethasone (RD), the time to disease progression was significantly longer for patients taking RD compared to those taking dexamethasone alone. On average, the time that patients receiving RD lived without their disease worsening was 12.1–13.9 months, compared with 4.7 months. Patients treated with RD had a 68%–72% improvement in time to progression compared to those treated with dexamethasone alone.

 

How is Revlimid currently being studied in myeloma?

Revlimid is being evaluated in a number of ongoing clinical trials in patients with newly diagnosed and relapsed and/or refractory myeloma, as well as in patients with asymptomatic high-risk smoldering multiple myeloma to see if it can delay progression to active myeloma (NCT01169337).

RVd is being evaluated alone and in combination with high-dose chemotherapy and ASCT in a phase 3 trial in newly diagnosed myeloma. Results from this trial will help determine if transplant is still necessary in the initial management of myeloma in younger patients or whether novel agents alone provide similar outcomes (NCT01191060).

Interested in learning more about Revlimid clinical trials? Talk to an  an MMRF Nurse Patient Navigator to learn more or use our clinical trials finder.

FIND CLINICAL TRIALS

Updated March 2019

Please visit the sponsor’s official patient site for up-to-date information on Revlimid