CCR Grand Rounds October 11: Dr. Phillip A. Sharp, Director, McGovern Institute for Brain Research, Center for Cancer Research, Massachusetts Institute of Technology; "The Surprising Biology of Short RNAs" October 18th: No Lecture. NIH Research Festival October 17-21 October 25: Dr. Angela Brodie, Professor of Pharmacology and Experimental Therapeutics, Department of Pharmacology, University of Maryland School of Medicine; "Aromatase Inhibitors and Breast Cancer: Concept to Clinic" CCR Grand Rounds are held 8:30 to 9:30 a.m. at the NIH campus in Bethesda, Md., in the Clinical Center's Lipsett Amphitheater.

In June of this year, NCI's Press Office hosted a Science Writers' Seminar on the blood-borne cancers: leukemia, lymphoma, and multiple myeloma. While progress has been made in treating many types of leukemia and lymphoma, multiple myeloma remains resistant.

Multiple myeloma is caused by plasma cells - a type of white blood cell - forming tumors in bone marrow. This disease affects about 16,000 people in this country each year. While the cause is not known, this disease is most prevalent in the elderly, suggesting it may be related to a decline in the immune system with aging.

"Blood plasma cells typically make up less than 5 percent of the cells in the bone marrow," says Dr. Wyndham Wilson of the Lymphoma Therapeutics Section of the Metabolism Branch in NCI's Center for Cancer Research (CCR). "In multiple myeloma, tumor cells are overproduced and can make up between 10 to 80 percent of the cells in the bone marrow, crowding out the normal cells."

Because the normal bone marrow cells are displaced, multiple myeloma patients often suffer from anemia and decreased resistance to infection. Kidney damage can occur as a result of excessive myeloma protein or calcium (from bone destruction) in the blood. This may lead to weakened muscles, malaise, and fatigue. The tumor growth can form multiple bone lesions, usually in the pelvis, spine, ribs, and skull.

Patients are often initially treated with chemotherapy accompanied by support for anemia, renal failure, osteoporosis, bone pain, and infections. About 50 to 75 percent of patients respond to treatment for 2 to 3 years, but all eventually relapse. Following relapse, therapy may include high-dose chemotherapy followed by a bone marrow transplant, which can sometimes extend survival 4 to 5 years.

"We're always looking for new treatments that will improve outcomes," says Dr. Wilson. "There are some promising new drugs being tested in clinical trials, but we're also finding new uses for some old drugs."

One such drug is thalidomide, which was introduced in the 1950s as a sedative and treatment for morning sickness. However, after its use was linked to birth defects, it was withdrawn from the market. Thalidomide has now reemerged and is considered the first new agent to treat multiple myeloma in more than 30 years.

Thalidomide is used alone and in combination with other drugs, but many patients experience side effects such as severe numbness and tingling in the limbs. As a result, researchers are exploring similar agents that have fewer adverse effects. Recent clinical trials are evaluating lenalidomide (Revlimid), a derivative of thalidomide. Like thalidomide, it inhibits the growth of myeloma cells and formation of new blood vessels. The FDA granted a fast-track review to evaluate its effectiveness for treatment of multiple myeloma and other blood cell disorders known as myelodysplastic syndromes.

In 2003, FDA approved another new class of cancer drugs known as proteasome inhibitors for treatment of recurrent myeloma. Bortezomib (Velcade) blocks the action of proteasomes, enzyme molecules that regulate cell growth by breaking down proteins within cells. Bortezomib directly inhibits myeloma tumor cells, but also affects other bone marrow cells and pathways regulating cell growth and survival. Normal cells recover from treatment with bortezomib, while myeloma cells usually die. Recent clinical studies suggest that bortezomib might increase patient survival and be used as a first-line treatment for multiple myeloma.

"Both lenalidomide and bortezomib represent a new approach to the treatment of multiple myeloma," notes Dr. Wilson. "By targeting both the tumor cell and the bone marrow microenvironment, we can treat patients who have developed drug resistance. This may represent a new frontier for treating other blood cancers, such as lymphoma."

By Lynette Grouse

For more information about multiple myeloma and other cancers of the blood, go to NCI's BenchMarks Web site at http://www.cancer.gov/newscenter/benchmarks-vol5-issue3. The BenchMarks site highlights the research featured at the NCI Science Writers' Seminars. New articles are posted every 2 to 3 months. The BenchMarks site also features background information on selected cancer topics, along with photos, videos, and animated graphics. The "Science Behind the News" series features tutorials for educational use by life science teachers, medical professionals, and the interested public. They are available in PDF and PowerPoint formats that may be downloaded from the Web.