Related Pages Search for Clinical Trials NCI's PDQ® registry of cancer clinical trials. Multiple Myeloma/Other Plasma Cell Neoplasms NCI's gateway for information about multiple myeloma and other plasma cell neoplasms. Highlights from ASCO 2006 A collection of links to material summarizing some of the important clinical trial results announced at the 2006 annual meeting of the American Society of Clinical Oncology (ASCO).

Key Words

Multiple myeloma, thalidomide, melphalan, prednisone, stem cell transplant, the elderly. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary.)

Summary

Elderly patients with multiple myeloma who were treated with the drug thalidomide in addition to standard chemotherapy lived 15 to 21 months longer on average than patients who received either high doses of a standard drug followed by a stem cell transplant or standard chemotherapy alone. However, patients who took thalidomide had higher rates of side effects - particularly blood clots and tingling in the hands and feet - than patients who received the other therapies.

Source

American Society of Clinical Oncology annual meeting, Atlanta, Georgia, June 4, 2006 (see the meeting abstract).

Background

Multiple myeloma occurs when a type of white blood cell called a plasma cell starts reproducing uncontrollably. The excess plasma cells crowd out healthy blood cells in the bone marrow (the spongy tissue inside large bones), causing pain and gradually destroying the bone.

An estimated 16,570 Americans will be diagnosed with multiple myeloma in 2006 and about 11,300 people are expected to die of the disease. Age is the most significant risk factor. Only one percent of cases of this cancer are diagnosed in people younger than 40. Half of those diagnosed are over the age of 71.

The current standard first-line therapy for multiple myeloma in patients ages 65 and older is a combination of the drugs melphalan and prednisone (MP). For younger patients, the standard treatment is an intense dose of melphalan followed by a stem cell transplant. Because this form of high-dose treatment poses risks of infection, anemia, and damage to vital organs such as the liver, it is not offered as standard therapy to older patients in the United States.

In May 2006 the U.S. Food and Drug Administration (FDA) approved the drug thalidomide for use in combination with another drug, dexamethasone, to treat newly diagnosed multiple myeloma. Still infamous because of its association with severe birth defects in the 1960s, thalidomide has also shown activity against multiple myeloma that has come back or is no longer responding to other therapies. The drug appears to affect the blood supply that fuels the growth of tumors and may fight cancer in other ways, as well.

Because thalidomide can cause severe birth defects, the FDA has set up a special program to strictly control its usage in women who may become pregnant.

The Study

Researchers in France enrolled 447 patients aged 65 to 75 into this phase III trial. Patients were randomly assigned to one of three groups.

• One group was treated with MP alone.
• The second group received high-dose melphalan followed by a stem cell transplant.
• The third group received thalidomide in addition to MP (called MP-T).

The lead author of the study was Thierry Facon, M.D., of the University of Lille in France.

Results

After a median follow-up period of just over three years, overall survival averaged 53.6 months for patients treated with MP-T. This compared with 38.6 months for patients who received high-dose melphalan plus a stem cell transplant and 32.2 months for those treated with MP alone. These results were so compelling that researchers stopped the study ahead of schedule and offered patients in the two other study arms the opportunity to switch to thalidomide plus MP.

Patients treated with MP-T suffered higher rates of side effects than patients in the other two groups. Nearly half of all patients in this group had a severe loss of white blood cells. Twelve percent got blood clots, compared with 6.5 percent of patients who had a stem cell transplant and 5 percent of those treated with MP alone.

In addition, about 30 percent of all patients treated with MP-T experienced tingling in their hands and feet. Known as peripheral neuropathy, this side effect is common in thalidomide therapy and did not occur at all in the other two groups. In most cases, however, this side effect was not severe.

(Note: final results from the trial were subsequently published in the Oct. 6, 2007, issue of the Lancet; see the journal abstract.)

Comments

Although the addition of thalidomide to MP chemotherapy is not a cure for multiple myeloma, this study’s findings show that it does extend survival in elderly patients in whom other therapies have stopped working, Facon, the lead author, said. The increased risk of blood clots could be addressed by giving patients blood-thinning medications, he said, and lower doses of thalidomide could reduce the incidence of peripheral neuropathy.

The MP-T regimen will “potentially emerge as a standard of care for elderly patients with multiple myeloma,” said Michael Bishop, M.D., of the National Cancer Institute’s Center for Cancer Research. However, he cautioned that these results shouldn’t be generally applied to all multiple myeloma patients. “High-dose melphalan with a stem cell transplant should still be considered the standard of care for younger patients” with this disease.

What’s more, said Bishop, other agents under investigation might yet prove even better than MP-T: bortezomib (Velcade®) and lenalidomide (Revlimid®).

Bortezomib has been approved by the FDA for previously treated multiple myeloma patients. In studies, lenalidomide, which is chemically similar to thalidomide has shown effectiveness against multiple myeloma that has come back or has stopped responding to treatment. Lenalidomide may have fewer side effects than thalidomide, but both drugs are likely to continue to play a role in multiple myeloma therapy, Facon said.

Back to Top