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Q&A: Lenalidomide for Multiple Myeloma

CancerWise - February 2008

Large multi-center clinical trials in Europe and North America have shown that the combination of lenalidomide (Revlimid®) and dexamethasone (Decadrone®) increased survival compared with placebo-dexamethasone treatment for patients with multiple myeloma after a variety of other treatments had failed.

Answering questions about the drug combination and the research that proved its effectiveness against an incurable bone marrow cancer is Donna Weber, M.D., an associate professor in M. D. Anderson’s Department of Lymphoma and Myeloma and lead investigator on the North American clinical trial.

What is multiple myeloma?

Multiple myeloma is a cancer caused by the proliferation of defective plasma cells in the bone marrow. These rapidly multiplying cells cause tumors to form in the bones, and they also crowd out normal cells in the bone marrow, interfering with the production of red and white blood cells and platelets. Bones weakened by the tumors are prone to fracture.

About 20,000 people are diagnosed with multiple myeloma each year in the United States, and about 11,000 people die from the disease.

How has this cancer been treated traditionally?

The standard approach for years was high-dose chemotherapy to wipe out the bone marrow and the patient's blood supply, often followed by an autologous blood stem cell transplant in which a patient's own stem cells are removed and frozen then returned to the body after high-dose chemotherapy.

What is challenging with this treatment is that while the blood cells are being restored, a patient is subject to infection, bleeding and anemia.

How has the treatment changed?

In the last five or six years, we’ve had three new drugs approved, the first new medications in decades.

Thalidomide was the first. Most people remember it because prior to 1961 it was prescribed as a sedative to pregnant women to prevent morning sickness and later was found to cause birth defects.

Since then, research has shown that thalidomide launches a broad attack on multiple myeloma.

Thalidomide was found to:

  • Kill tumor cells directly
  • Undermine a tumor’s blood supply
  • Promote the body's tumor-fighting ability

Like many cancer drugs, thalidomide caused serious side effects for some multiple myeloma patients.

For example, peripheral neuropathy (nerve pain, tingling and numbness) could reach debilitating levels in some patients. The drug, like others that target blood cancers, also caused deficiencies of infection-fighting white blood cells or dangerous blood clotting.

How does lenalidomide differ from thalidomide?

As a result of the serious side effects of thalidomide, Celgene Corp., the company that makes thalidomide changed it in hopes of making it work as well as or better as thalidomide, with fewer side effects.

What were the results of the lenalidomide combination?

We tested lenalidomide with the steroid dexamethasone against dexamethasone plus placebo, and our results were reported late last year in the New England Journal of Medicine.

The North American trial included 353 patients in 44 cancer centers in the United States and Canada. All patients had relapsed or refractory multiple myeloma. They had received one or more previous treatments, including radiation therapy, stem cell transplants, various combinations of traditional chemotherapy drugs and the newer drugs, including thalidomide and bortezomib (Velcade®).

Patients who took the lenalidomide-dexamethasone combination had a median time to disease progression of 11.1 months, compared with 4.7 months in the dexamethasone-placebo group. Median overall survival time also was better at 29.6 months compared with 20.2 months.

Of the 177 patients who received the combination, 108 (61%) had complete, near-complete or partial responses, compared with 35 patients out of 176 in the placebo group. Nearly identical results were reported in a cooperative international trial by a previous M. D. Anderson faculty member, Meltios Dimopoulos, M.D., now at the University of Athens.

An interim data analysis showed that the results were so good that the trial was halted to allow patients on placebo to receive the lenalidomide combination. The U.S. Food and Drug Administration approved this combination for previously treated multiple myeloma patients based on this clinical trial.

What were the side effects?

High-grade peripheral neuropathy occurred in just 1.7% of patients on the lenalidomide combination. High-grade constipation and diarrhea occurred in only 2.8% and 3.4% of patients, respectively.

However, 41.2% experienced significant suppression of their white blood cells, making them vulnerable to infection. In most cases infections were able to be managed by administering antibiotics or decreasing the lenalidomide dose. Also, 14.7% of patients experienced blood clots that were treated with anticoagulants, allowing most patients to continue receiving lenalidomide-dexamethasone in the trial.

Any other interesting findings?

A sub-analysis by Michael Wang, M.D., an assistant professor in the Department of Lymphoma and Myeloma, found that 56.8% of patients who developed a resistance to thalidomide responded to the lenalidomide combination. That suggests these two drugs differ enough to produce a separate disease response, not just a different side-effect profile.

The combination also worked for the minority of patients who had previously taken bortezomib, another new drug, and then relapsed.

It’s fantastic that these clinical trials brought an effective new drug to offer our patients. But they've accomplished so much more in reality.

A new drug often works well in combination with other new or even traditional chemotherapy drugs, restoring activity of these drugs against cancers that have previously become resistant to them. So now we have more combinations to offer our patients, many of which are being tested in clinical trials.

Lenalidomide also is being tested as frontline therapy, the first treatment that new patients receive.

One last word, multiple myeloma researchers across the country and internationally began to work together years ago to combine efforts to speed new therapies to our patients. These two clinical trials show how large-scale cooperation in a team effort can quickly confirm the benefits of a new drug and introduce it to patients with this disease.

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© 2014 The University of Texas MD Anderson Cancer Center