Lenalidomide Effective in Multiple MyelomaKey Words
Multiple myeloma, lenalidomide>, dexamethasone. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary.)
Summary
Combining a new drug called lenalidomide with a standard drug, dexamethasone, delayed the progression of advanced multiple myeloma for more than twice as long as did dexamethasone alone in patients whose disease had come back or stopped responding to other treatments. Patients benefited from lenalidomide whether or not they had previously been treated with its chemical cousin thalidomide.
Source
American Society of Clinical Oncology (ASCO) annual meeting, Atlanta, Georgia, June 5, 2006.
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.
For the 1 percent of multiple myeloma patients younger than 40, the standard treatment is intensive chemotherapy followed by a stem cell transplant. This form of high-dose treatment poses risks of infection, anemia, and damage to vital organs such as the liver. High doses of steroids such as prednisone or dexamethasone are also commonly used.
Chemotherapy, often including the oral drug thalidomide, can put some patient’s disease into remission. However, most therapies for multiple myeloma eventually lose their effectiveness. Researchers are still looking for the best way to treat patients whose disease has come back (recurrent disease) or stopped responding to therapy (refractory disease).
Lenalidomide is a new drug that is chemically similar to thalidomide but may be more potent and have fewer adverse effects. Like thalidomide, lenalidomide can cause severe birth defects. For this reason, the U.S. Food and Drug Administration (FDA) has set up a special program to strictly control its usage in women who may become pregnant.
Study 1 (MM-009)
Researchers in the United States and Canada enrolled 354 patients with multiple myeloma that had come back or stopped responding to treatment.. All patients on this phase III study (called MM-009) had received previous treatment with a steroid, usually dexamethasone or prednisone. Two-thirds had had a stem cell transplant and nearly half had been treated with thalidomide.
Patients were randomly assigned to treatment with either lenalidomide plus high-dose dexamethasone (Len-Dex) or high-dose dexamethasone plus a placebo. The primary goal of the study was to measure how long it took for the disease to progress in the two groups of patients. The researchers also measured how many patients responded to treatment and how long patients lived.
The lead author of the study was Donna M. Weber, M.D., of Princess Margaret Hospital in Toronto, Canada (see the meeting abstract).
Study 1 Results
Disease progression was delayed for a median of 11.1 months in patients who received Len-Dex, compared with 4.7 months for patients treated with dexamethasone plus a placebo. Patients’ disease responded to treatment in 59.4 percent of patients treated with Len-Dex but in just 21.1 percent of patients who received dexamethasone and a placebo.
The median overall survival rate for the Len-Dex group wasn’t available at the time the study data were analyzed. Median overall survival in the dexamethasone-plus-placebo group was 24 months.
Patients who took lenalidomide had many of the same side effects seen with those taking thalidomide in other studies, but at lower levels, Weber said. Rates of side effects such as tingling in the hands and feet, constipation, and fatigue “appear to be less [with lenalidomide] than with thalidomide,” said Weber.
The number of patients suffering abnormal blood cell counts was higher in the lenalidomide group than has been seen in studies of thalidomide, she continued, adding that this side effect can be managed by reducing the dose of lenalidomide.
Fifteen percent of patients in the lenalidomide group got blood clots, compared with 3.5 percent in the dexamethasone-plus-placebo group. This side effect occurred with the same frequency in patients taking lenalidomide as it has in patients taking thalidomide in other studies, Weber said.
In the Len-Dex group, 17 percent of patients dropped out of the study because of side effects. This compared with nine percent of patients in the dexamethasone-plus-placebo group. By contrast, 35 percent of patients in the Len-Dex group withdrew from the study because of disease progression, compared with 70 percent of those taking dexamethasone and a placebo.
(Note: Final results from the MM-009 trial were subsequently published in the Nov. 22, 2007, New England Journal of Medicine; see the journal abstract.)
Study 2 (Previous treatment with thalidomide)
In the second study described here (Study 2), researchers analyzed combined data from the North American MM-009 study (Study 1, above) and an identical European study (MM-010) that had taken place at the same time. Like the North American study, the European MM-010 found that patients whose multiple myeloma had advanced after initial therapy did significantly better when treated with lenalidomide plus dexamethasone compared to dexamethasone alone.
The primary goal of Study 2, however, was to learn whether the 692 patients evaluated from these two trials were less likely to benefit from lenalidomide if they had been previously treated with its chemical cousin thalidomide.
The lead author for this study was Michael Wang of the University of Texas M.D. Anderson Cancer Center in Houston (see the meeting abstract).
Study 2 Results
The analysis showed that regardless of whether patients had been previously treated with thalidomide, the Len-Dex combined regimen was more effective at stalling the progression of the disease than dexamethasone plus a placebo.
(Note: Final results from the MM-010 trial were subsequently published in the Nov. 22, 2007, New England Journal of Medicine; see the journal abstract.)
Comments
These studies show that Len-Dex “is an excellent new treatment option for patients with recurrent or refractory multiple myeloma,” said Michael Bishop, M.D., a multiple myeloma specialist with the National Cancer Institute’s Center for Cancer Research.
Patients who had been previously treated with thalidomide received slightly less benefit from Len-Dex than those who had not, Bishop noted, but they still did markedly better than patients who received dexamethasone alone.
(Note: Pooled data from these two trials concerning patients with prior exposure to thalidomide was subsequently published online Sept. 17, 2008, in Blood; see the journal abstract.)
Limitations
These studies did not address the question of whether lenalidomide is superior to thalidomide, Bishop said. That would require a randomized trial in which the two drugs were compared head to head.
Another new drug, bortezomib (Velcade®), has been approved by the FDA for treatment of previously treated multiple myeloma. The studies described here do not address the order in which it is best to give thalidomide, lenalidomide, and bortezomib to patients with advanced multiple myeloma, Bishop said.
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