A thalidomide derivative plus dexamethasone improved outcomes, studies found
WEDNESDAY, Nov. 21 (HealthDay News) -- A combination drug regimen that includes a derivative of thalidomide extended survival, as well as the time it took for the disease to reappear, in patients with multiple myeloma.
The combination of Revlimid (lenalidomide) and dexamethasone was given U.S. Food and Drug Administration regulatory approval in June of 2006 for multiple myeloma patients who had already failed one treatment.
Now, two papers, appearing in the Nov. 22 issue of the New England Journal of Medicine, mark the final publications of the study that paved the way for that approval, said Hildy Dillon, vice president of patient services disease programs at the Leukemia & Lymphoma Society in White Plains, N.Y.
"People who got [the combination regimen] had three times the likelihood of responding," added Dr. Donna M. Weber, lead author of the North American segment of the study and associate professor of medicine at M.D. Anderson Cancer Center in Houston. "Overall survival showed a nine-month improvement from 20.2 to 29.6 months," she said.
Multiple myeloma is a cancer of the blood's plasma cells that causes almost 11,000 deaths each year in the United States. Experts say the new findings -- along with the recent FDA approval of the drug combo -- should greatly broaden the treatment landscape for multiple myeloma, which historically has been a difficult disease to treat.
Revlimid is a derivative of thalidomide, with alterations in its chemistry that give it more potency with fewer side effects, experts explained.
Thalidomide first appeared in Europe in the 1950s to treat morning sickness in pregnant women. Between 1956 and 1962, however, some 10,000 children were born with severe birth defects as a result of their mother having taking the drug.
But more recently, the drug has shown some benefit against various disorders including multiple myeloma and syndromes related to HIV infection.
Multiple myeloma "tends to relapse and, in the past, there have not been many options for therapy other than stem cell transplant, which can be very rigorous and high risk for patients," Dillon said. "This is a disease that is very common, more common in older adults than in younger people, where the risk of transplant is higher than it even is in younger population."
Thalidomide had shown benefits against multiple myeloma, but side effects of fatigue, neuropathy, constipation and blood clots were severe.
The first study took place in Canada and in the United States and involved 353 patients who had undergone at least one previous therapy for their disease. Participants were randomized to receive either 25 milligrams of Revlimid or a placebo for the first three weeks. Both groups received dexamethasone on days 1 to 4, 9 to 12 and 17 to 20 of the first four cycles.
Sixty-one percent of participants receiving the combination therapy had complete, near complete or partial responses, versus only 19.9 percent in the placebo group. In the combination group, 14.1 percent had complete responses, compared with 0.6 percent in the placebo group.
Median time to progression of the disease was also longer in the combination group: 11.1 months versus 4.7 months for those on placebo.
Median survival was 29.6 months in the Revlimid group and 20.2 months in the placebo group.
High-level side effects were seen in 85.3 percent of the Revlimid group and 73.1 percent of the placebo group. More people in the Revlimid group had neutropenia (a lowering of white blood cells) and blood clots.
"We showed that lenalidomide minimized neuropathy but blood clots still remained an issue, so people still need to have some form of anti-thrombotic medicine with this drug," Weber said.
The second study, a multicenter effort led by Dr. Meletios Dimopoulos of the University of Athens, Greece, involved 351 patients in Europe who were randomized to the same protocol.
Results were essentially identical to the North American arm.
"These newer drug therapies and drug combinations are enabling people to live with their diseases longer, to possibly get a good response, then there might be a good combination later on that they can try," Dillon said. "It's good news to have another drug in the arsenal of this disease, which can be very difficult to treat."
There's more on multiple myeloma at the Leukemia & Lymphoma Society .
SOURCES: Donna M. Weber, M.D., associate professor, medicine, M.D. Anderson Cancer Center, Houston; Hildy Dillon, vice president, patient services disease programs, Leukemia & Lymphoma Society, White Plains, N.Y.; Nov. 22, 2007, New England Journal of Medicine
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