Mayo Clinic Cancer Center investigators report that combination therapy with lenalidomide (Revlimid) and dexamethasone (combination is called Rev/Dex) looks like a breakthrough treatment for multiple myeloma. Results of a Phase II clinical trial were published online Aug. 23 in Blood.
"Previous studies have shown Rev/Dex to be effective for recurrent or highly resistant forms of myeloma," says S. Vincent Rajkumar, M.D., Mayo Clinic hematological oncologist and lead investigator of the study, "In this study, the first one to use the combination as initial therapy in newly diagnosed patients, we find that the Rev/Dex combination reduced the myeloma cancer protein levels by more than half in 91 percent of patients - much higher than response rates obtained with current approved therapies."
The goal of this clinical trial was to determine the response rate and toxicity (type and severity of side effects) of Rev/Dex in patients with previously untreated, newly diagnosed multiple myeloma. Over the course of the trial, 34 patients underwent the combination treatment, with 31 (91 percent) showing positive response to the treatment, and all within a rapid period - average response time was one month. In addition to the quick and positive responses, side effects were manageable, and common ones associated with thalidomide treatment, such as constipation, blood clots and neuropathy, were uncommon. Rev/Dex is administered orally - making it a more attractive option to many patients compared to traditional intravenous treatments.
"We see this as potentially the way of the future for many myeloma patients," says Morie Gertz, M.D., Mayo hematological oncologist and co-investigator, "We are happy that two large Phase III trials are currently ongoing, moving forward the testing of Rev/Dex as initial therapy for myeloma."
Multiple myeloma is a malignant cancer of the blood that causes 11,000 deaths each year. Standard therapy of melphalan and prednisone results in about 50 percent of patients having a positive response - i.e. the cancer cells lessen by more than half. Vincristine, doxorubicin and dexamethasone (VAD) is another chemotherapy regimen used to treat myeloma, typically for patients who are candidates for stem cell transplantation because it allows adequate and safe stem cell harvest during treatment for a future transplantation. However, the use of VAD chemotherapy has decreased greatly because of the need for intravenous therapy and the need for a catheter - bringing other potential health risks.
Recent studies have looked at the oral combination of thalidomide and dexamethasone (Thal/Dex) as an alternative to VAD. Although response rates are excellent (approximately 70 percent), the combination causes significant side effects. Lenalidomide is a compound similar to thalidomide, but one which previous studies have shown to work better both for recurrent and highly resistant myelomas, both alone and in conjunction with dexamethasone. It has fewer side effects than thalidomide and has even caused improvement in patients who are nonresponsive to thalidomide.
Lenalidomide is not commercially available; approval by the Food and Drug Administration is pending. The study was funded with grants from the National Cancer Institute and Celgene Corporation, which manufactures Revlimid.