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Treating Multiple Myeloma From Every Angle

New treatments for multiple myeloma target the disease in different ways.

BY HEATHER L. VAN EPPS, PHD
PUBLISHED TUESDAY, JUNE 18, 2013
In November 2008, entertainment producer Sean Murray, of Kimberling City, Mo., developed a backache that went "from annoying to excruciating" in a matter of days. After examining X-rays of his back and right shoulder, Murray’s doctor immediately suspected cancer. A full-body imaging scan revealed an 8.5-centimeter lesion on Murray's right shoulder as well as lesions on his ribs, spine and pelvis. A blood test confirmed that Murray, then 49, had multiple myeloma, a blood cancer that often causes painful bone lesions.

"I have a high threshold for pain," says Murray, explaining that he'd coped with pain in his right shoulder for more than a year before receiving his diagnosis. "But soon the house of cards started to fall."

By the time Murray started treatments, three of his vertebrae had collapsed, and he had a tumor pressing dangerously on his spinal cord. His doctors recommended that he start treatment immediately, but first Murray wanted to see his two young daughters. "At this point, we didn’t know if I was going to live," he says, "so I wanted to go home for Thanksgiving and surprise my daughters."

After the holiday, Murray embarked on a treatment journey that included a procedure to repair his vertebrae, aggressive combination chemotherapy, two autologous stem cell transplantations and three years of lower dose “maintenance” chemotherapy. By November of last year, Murray went off all his myeloma medications. To date, his disease is stable.

Although most oncologists consider multiple myeloma incurable, the survival rate has doubled in the past two decades, thanks to the development of more effective therapies. And with new drugs recently approved for multiple myeloma and others in the clinical trials pipeline, the outlook for these patients is getting even brighter.

About 22,000 Americans receive a diagnosis of multiple myeloma each year. It is more common in people over age 65, men and African-Americans. The disease arises in immune cells called plasma cells—specialized types of white blood cells that normally produce infection-fighting antibodies. The cancerous plasma cells produce abnormally high levels of a nonfunctional antibody, called M (monoclonal) protein, which can be detected in the blood or urine. Some people have elevated M protein in their blood but no other symptoms of multiple myeloma, such as bone pain, fatigue and anemia. These individuals have a pre-cancerous condition known as monoclonal gammopathy of undetermined significance (MGUS) and are not treated, although roughly 12 to 30 percent of these individuals will eventually develop multiple myeloma (most commonly), amyloidosis (a buildup of protein in multiple organs), lymphoma or chronic lymphocytic leukemia.

Patrick Killingsworth, a former real estate agent from Weeki Wachee, Fla., was told he had stage 3 multiple myeloma in 2007 at age 51. Killingsworth had always been physically active but noticed more aches and pains over the years, eventually developing severe hip pain that affected his ability to walk. "I sneezed in the shower one morning and the [back] pain was so bad I couldn't move," Killingsworth recalls. An imaging scan revealed lesions in his hips and spine.

I sneezed in the shower one morning and the [back] pain was so bad I couldn't move.

The International Staging System for multiple myeloma is based on blood levels of two proteins called beta-2 microglobulin and serum albumin, with high levels of the former indicative of more advanced disease regardless of serum albumin levels. Certain genetic abnormalities, including amplifications, deletions and rearrangements of specific chromosomes, are also associated with higher-risk disease. Although both Murray and Killingsworth received a diagnosis of stage 3 disease, neither had any of the genetic risk factors associated with a poor outcome.

Disease stage and risk factors play into prognosis, as well as treatment sequencing. After determining a patient's transplantation eligibility, the first step for virtually all patients is high-dose "induction" chemotherapy, the goal of which is to induce remission. For transplantation-eligible patients, this usually involves treatment with two types of anticancer drugs—immunomodulatory drugs and proteasome inhibitors—in combination with the steroid dexamethasone. Patients too old or sick to tolerate transplantation are still treated with combination therapy, often the same combinations as used for induction chemotherapy.

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