Maintenance therapy with Revlimid was shown to increase progression-free… (National Institutes of…)
Lenalidomide, sold under the tradename Revlimid, significantly improves progression-free survival in patients with myeloma, according to three clinical trials published Wednesday. All three trials were so successful that the results were unblinded early and, in two of the three trials, patients receiving the placebo were switched to the active drug. But researchers also found that the drug doubled the risk of a second, independent cancer occurring, and it is not yet clear whether the drug produces an increase in overall survival. Moreover, the drug is quite expensive, more than $163,000 for a year of treatment, and there was no data indicating whether quality of life improved enough to justify the cost.
Multiple myeloma is a result of the accumulation of plasma cells -- a form of white blood cells -- in the bone marrow, where they interfere with production of healthy blood cells. It affects between 1 and 4 of every 100,000 people and accounts for about 1% of all U.S. cancers. It is more common in men than in women, and twice as common in blacks as in whites. Average survival is about three to four years, but newer treatments, such as high-dose drug therapy and bone-marrow transplants can extend survival to as long as seven years.
Researchers have been working to maintain remission after the initial treatment with drugs and transplants, known as maintenance therapy, but previous results were hindered by their toxic side effects and their failure to prolong survival. Thalidomide increased both progression-free survival and overall survival, but it was poorly tolerated and many patients stopped using it.
Lenalidomide is the next hope for maintenance therapy. It is an immune-modulating agent that kills abnormal cells in the bone marrow and helps bone marrow produce healthy cells.
Separate teams in France, Italy and at the Roswell Park Cancer Institute in Buffalo, N.Y., conducted clinical trials on patients who had undergone an initial remission. Two of the groups studied patients who had a bone-marrow transplant, giving those in remission either lenalidomide or a placebo. The third group studied patients who were ineligible for transplants, but who achieved initial remission with a combination of melphalan, prednisone and lenalidomide.
The teams reported in the New England Journal of Medicine that progression-free survival in the transplant patients increased from 21 months to 39 months in one group and from 23 months to 41 months in the other. In the group ineligible for transplants, progression-free survival increased from 14 months with placebo to 31 months with lenalidomide; in a subgroup that received maintenance therapy with melphalan and prednisone, the average was only 14 months. Three-year survival in all three trials ranged from 70% to 88%.
In an editorial in the same issue of the journal, Dr. Ashraf Z. Badros of the University of Maryland School of Medicine speculated that overall survival might improve with the drug once patients have been followed longer.
Side effects of the drug were manageable, but 9% to 27% of patients dropped out of the study because of problems. "The most surprising finding," Badros said, was a 7% to 8% incidence of second primary cancers in the lenalidomide groups compared with 3% to 4% in the placebo groups. Second cancers are a known risk with myeloma because of the use of potentially carcinogenic drugs to treat it, but this rate was unexpectedly high. Nonetheless, Badros said, the improved survival period in all three trials seems to outweigh the risk of secondary cancers.
Two of the studies were partially supported by Celgene, which manufactures Revlimid. The third was sponsored by the National Cancer Institute.