New drugs offer hope in treating cancer of the blood

In multiple myeloma, the bone marrow has an
excessive number of
abnormal plasma cells.

MILWAUKEE JOURNAL SENTINEL

MILWAUKEE — A better understanding of plasma cells and how they act inside bone marrow has enabled scientists to improve dramatically treatment of patients with the blood cancer multiple myeloma.

In the past decade, they’ve tweaked old drugs and created new ones to either slow or stabilize tumor growth. As a result, patients live longer and doctors have become increasingly hopeful that the often fatal and incurable disease soon will be treated more like a chronic condition.

“It’s like night and day,” said Mitchell Smith, director of the lymphoma service at Fox Chase Cancer Center in Philadelphia, who’s been treating patients with multiple myeloma for almost 20 years.

“When I started practicing, you’d tell patients they’d have problems with bone fractures and bone pain and chemotherapy side effects,” he said. “Then you’d say, ‘You need a stem-cell transplant and even with that, the disease will stay away awhile before coming back, and there won’t be much more that we can offer you.’”

But the recent approval of three drugs for multiple myeloma treatment — thalidomide, lenalidomide and bortezomib — and the testing of several others in clinical trials have changed the outlook for most patients, Smith said. He is also a member of a committee that develops the multiple myeloma clinical practice guidelines set by the National Comprehensive Cancer Network.

Multiple myeloma is a cancer characterized by an excessive number of abnormal plasma cells in the bone marrow. Plasma cells play a major role in the immune system because they produce antibodies to fight infections and disease. When they grow out of control, plasma cells can form a tumor, usually in the bone marrow.

This means that the bone marrow may not be able to make enough red blood cells, platelets or normal white blood cells. As a result, patients can become anemic, more susceptible to infections and bleeding, and develop bone damage.

In rare cases, the disease can lead to organ damage, particularly in the kidneys.

The American Cancer Society estimates that there will be about 19,900 new cases and 10,790 deaths from multiple myeloma in 2007. The disease is more common in men and blacks.

For years, multiple myeloma was treated with chemotherapy in combination with hematopoietic stem cell transplantation, which uses the cells found in adult bone marrow.

But now, patients typically receive some form of initial therapy such as the steroid dexamethasone in combination with thalidomide or lenalidomide, as well as treatment for bone disease and other complications.

“It’s a very exciting time because we have lots of drugs (that) basically change the bone marrow environment and make it hard for cancer cells to live there,” said Parameswaran Hari, an assistant professor of medicine at the Medical College of Wisconsin and a myeloma specialist at Froedtert Hospital.

In May 2003, Velcade, or bortezomib, became the first new treatment in more than a decade. It slows the progression of the disease in patients who have relapsed after two prior treatments and who have shown resistance to their last treatment. The Food and Drug Administration approved the drug in less than four months.

Three years later, the agency approved Revlimid, or lenalidomide, to delay cancer progression in patients who had failed previous therapy.

The drug works similar to the cancer drug thalidomide, which caused thousands of birth defects in the 1960s, but it has fewer side effects. Thalidomide was also approved in 2006 for use in combination with the dexamethasone for initial treatment in patients diagnosed with multiple myeloma.

Patients taking either lenalidomide or thalidomide must comply with a carefully monitored program developed by the FDA.

The expanded choices are a boon for patients, but they also make it difficult for doctors to determine where to start treatment because there are now so many right choices, said Natalie Callander, an associate professor of medicine and an oncologist at the University of Wisconsin Carbone Cancer Center in Madison.