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Preventing Smoldering Multiple Myeloma from Progressing

Name of the Trial

Phase II Trial of IPH2101 (Anti-KIR) in Smoldering Multiple Myeloma (SMM) (NCI-11-C-0024). See the protocol summary.

Principal Investigator

Dr. Ola Landgren, NCI Center for Cancer Research

Dr. Ola Landgren
Principal Investigator

Why This Trial Is Important

Multiple myeloma is an often-deadly cancer in which abnormal plasma cells accumulate in the bone marrow. Despite recent advances in treatment, the disease remains incurable. Consequently, doctors are eager to find ways to prevent it in people at high risk.

Multiple myeloma is characterized by a marker in the blood (and/or urine) called monoclonal protein (also called M protein), bone lesions, anemia, kidney failure, hypercalcemia, or a combination of these symptoms. The detection of M protein in the blood without evidence of bone lesions or organ damage indicates the presence of one of two precancerous conditions that carry differing risks of progression to multiple myeloma. One of these conditions, called monoclonal gammopathy of undetermined significance, or MGUS, has on average, a low risk of progressing to multiple myeloma. In contrast, patients with smoldering myeloma, have on average, a much higher risk of developing multiple myeloma.  

Typically, doctors manage patients with MGUS or smoldering myeloma using an active surveillance strategy that involves varying degrees of monitoring based on the presence of certain risk factors. There are no standard treatment options for people with these conditions. However, experts in multiple myeloma research are beginning to approach the conditions differently, with more aggressive monitoring of those with high-risk MGUS and smoldering myeloma.

Based on current knowledge, the average time of progression from high-risk smoldering myeloma to multiple myeloma is less than 2 years. Researchers have begun to investigate whether treating people with smoldering myeloma with novel strategies can help delay or prevent some of them from developing multiple myeloma.

Treatment of smoldering myeloma with therapies that are used to treat multiple myeloma is complicated by the fact that current treatments for multiple myeloma carry risks of severe side effects that may outweigh the potential benefits. Nevertheless, some clinical trials are being conducted to compare the use of common myeloma drugs, such as lenalidomide, with surveillance alone. Although early results suggest this approach may be beneficial, it’s too early to tell if treatment is truly preventing progression or only delaying it. Researchers at NCI are pursuing a different approach that they hope will help those with smoldering myeloma while bypassing some of the side effects commonly associated with aggressive therapy.

In this trial, people diagnosed with smoldering myeloma will be treated with an experimental biological agent called IPH2101 that helps immune cells called natural killer cells, or NK cells, attack and destroy myeloma cells. NK cells normally have the ability to destroy myeloma cells, but myeloma cells can trigger receptors on the surface of NK cells, called KIR receptors, that deactivate the immune response of NK cells against myeloma cells. IPH2101 is a monoclonal antibody that attaches to and blocks KIR receptors, so myeloma cells cannot use this mechanism to turn off an NK-cell attack.

“Our recent investigations show that virtually all patients who develop frank multiple myeloma go through a period of asymptomatic disease (MGUS and smoldering myeloma); so, if we can catch it then, I believe that may give us the best chance to cure some of them," said Dr. Landgren.

“Our tests in people participating in the study show that [IPH2101] binds to the NK cells at an extremely high rate," so it should be very effective in preventing the tumor cells from deactivating the NK cells, Dr. Landgren explained. “So far, we’ve seen no serious side effects in participants receiving the drug. At NCI, we are developing several novel treatment studies for patients diagnosed with smoldering myeloma or multiple myeloma."

For More Information

See the lists of eligibility criteria and trial contact information or call the NCI Clinical Trials Referral Office at 1-888-NCI-1937. The call is toll free and confidential. Also see the NCI’s Multiple Myeloma Clinical Research Section Web site.

  • Posted: July 12, 2011