In the study, 353 patients with myeloma received either a combination of lenalidomide (Revlimid(r)) and the steroid dexamethasone or dexamethasone plus a placebo.
"Those taking the lenalidomide combination had a median time to disease progression of 11.1 months compared with 4.7 months in the placebo-dexamethasone group and an improved median overall survival time of 29.6 months compared with 20.2 months," said lead author Donna Weber, M.D., associate professor in the Department of Lymphoma and Myeloma at The University of Texas M. D. Anderson Cancer Center.
The results were impressive enough that in December of 2005 an independent interim data analysis resulted in the trial being halted early so those on placebo-dexamethasone could also benefit from the addition of lenalidomide.
The collaborative study by North American Multiple Myeloma Study Investigators, and an international trial led to the approval of lenalidomide and dexamethasone for previously treated patients by the U.S. Food and Drug Administration in 2006.
"These trials highlight how large-scale cooperation in a team effort by myeloma investigators can quickly confirm benefits and introduce new active agents for patients with this disease. We also owe a debt to the willing patients who participated in this study," Weber said.
Thalidomide, a breakthrough drug for multiple myeloma, is produced and marketed by Celgene Corporation as Thalomid. The company chemically altered thalidomide to make lenalidomide, known commercially as Revlimid, in hopes of reducing side effects and improving efficacy against the disease. The drugs attack both the malignant cells and the cellular environment that nurtures them.
Of 177 patients who received the lenalidomide combination therapy, 108 (61 percent) had complete, near-complete or partial responses to the medication compared with 35 patients out of 176 (19.9 percent) in the placebo-dexamethasone group.
Michael Wang, M.D., assistant professor in the Department of Lymphoma and Myeloma at M. D. Anderson conducted an analysis and found 56.8 percent of patients who had prior treatment with thalidomide before receiving the lenalidomide combination had a response, compared with 64.1 percent with no previous thalidomide treatment.
"That suggests that the drugs differ enough to get a separate response, not just a refinement of side effects," Weber said.
The superior results for the combination also held up among patients previously treated with another new drug, bortezomib, a proteasome inhibitor known commercially as Velcade and marketed by Millennium Pharmaceuticals.
Combinations of drugs are important in ongoing treatment as a patient's disease becomes resistant to one therapy.
"It's great that this research gave us a new drug. But what we also find with new drugs is that they work well with older therapies, which gives us many combinations to offer our patients." Weber said.
Lenalidomide is being tested as a front-line therapy and in combination with other medications in a variety of clinical trials.
Overall, 85.3 percent of those receiving the combination therapy experienced side effects compared with 73.1 percent of the placebo-dexamethasone group. Some of the side effects were serious enough to cause 19.8 percent of the combination group and 10.2 percent of the placebo group to quit the trial.
Major side effects from the combination were suppression of patients' white blood cells, making them vulnerable to infection, and formation of blood clots. In most cases, these side effects were countered by decreasing the lenalidomide dose, or administering antibiotics or anticoagulants.
One of the major side effects of thalidomide - significant nerve pain and numbness in the limbs known as peripheral neuropathy - was nearly absent in the lenalidomide group.
The new study is published in the Nov. 22 New England Journal of Medicine.