Mayo Clinic -- Collaborating To Move Treatment Research Forward

Main Category: Lymphoma / Leukemia / Myeloma
Also Included In: Cancer / Oncology;  Blood / Hematology
Article Date: 16 Dec 2006 - 12:00 PDT

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Novel therapies are greatly improving the long-term outlook for patients with multiple myeloma, say researchers at Mayo Clinic Cancer Center, who have led efforts in testing these treatments and moving them quickly into first-line therapies.

At the 2006 American Society of Hematology (ASH) Annual Meeting, these investigators presented results from five studies that tested new therapies in myeloma in order to improve effectiveness and reduce toxicity. The primary treatments being studied are the agents thalidomide (Thalomid), lenalidomide (Revlimid), and bortezomib (Velcade), that disrupt the microenvironment -- the cellular habitat -- of the tumor. Lenalidomide and bortezomib are approved by the U.S. Food and Drug Administration (FDA) for treatment of relapsed myeloma. Earlier this year the FDA also granted accelerated approval for thalidomide use in patients with newly diagnosed myeloma, based on a cooperative group clinical trial led by Mayo Clinic investigators.

"These treatments represent a revolutionary approach to the care of patients with multiple myeloma, especially in those who are newly diagnosed," says S. Vincent Rajkumar, M.D., hematologist at Mayo Clinic in Rochester, Minn., and lead author of some of the studies presented.

Multiple myeloma, a cancer of plasma cells, is the second most common blood cancer in the United States, diagnosed in about 15,000 people annually. As yet, no cure exists for the disease, and average survival has been about three to four years, says Dr. Rajkumar.

The studies presented at ASH are the latest updates of clinical trials led by Mayo investigators. One study was a large (470 patients) Phase III double-blind clinical trial of thalidomide plus dexamethasone (Thal/Dex) versus placebo plus dexamethasone (placebo/Dex). The Thal/Dex combination resulted in a significantly higher response rate (63 percent) compared to placebo/Dex (46 percent). A tumor load reduction (lessening of cancerous cells) of 90 percent or greater was seen in 44 percent of Thal/Dex patients versus 16 percent in placebo/Dex-treated patients. Additionally, the time it took for the myeloma to progress was substantially longer in the Thal/Dex arm (24 months) versus treatment with placebo/Dex (six months). "Our results show that targeting both the tumor cells and the tumor"s microenvironment may have a synergistic effect," says Dr. Rajkumar, who led the international trial. He notes that patients are still being followed to assess survival differences.

Although the above results are promising, even better outcomes may be possible by using lenalidomide, potentially a safer and more effective analogue (cousin) of thalidomide, says Martha Lacy, M.D., a hematologist at Mayo Clinic in Rochester. She presented the latest results of a Phase II Mayo Clinic trial testing lenalidomide plus dexamethasone (Rev/Dex) in 34 patients with newly diagnosed myeloma. The researchers found that 64 percent of the patients achieved more than a 90 percent drop in the amount of cancerous cells. Further, there seemed to be fewer side effects with use of Rev/Dex, compared to what is usually seen with Thal/Dex. At two years of follow-up, the progression rate among patients is low -- 74 percent have not yet experienced renewed disease progression, reports Dr. Lacy. "These are the best results we have seen so far," she says.

To reduce the toxicity from Rev/Dex, which mainly results from the high dose of dexamethasone, a large Eastern Cooperative Oncology Group (ECOG) study was launched to compare two different doses of dexamethasone in combination with lenalidomide. "The high dose of dexamethasone puts patients at an increased risk of developing blood clots and other side effects," says Dr. Rajkumar, who is leading the study and presenting the results. "We can"t do without this drug, but we want to see if we can reduce the dose to be safer."

In a Phase III ECOG trial that enrolled 445 patients, results so far show that toxicity rates are much higher in the high-dose arm. More than 53 percent of patients on the high-dose therapy experienced grade 3 or higher toxicities, compared to 36 percent using the lower dose. Results of response to therapy between the two arms of the trial are expected next year.

In addition to the three studies above, Mayo researchers also reported on the use of lenalidomide in combination with melphalan and prednisone (MPR) in elderly patients who typically cannot take high-dose dexamethasone. MPR appears effective in these patients, according to interim results presented by Vivek Roy, M.D., a hematologist at Mayo Clinic in Jacksonville, Fla.

Finally, an ECOG-coordinated study led by Angela Dispenzieri, M.D., a Mayo Clinic hematologist, showed that bortezomib offers the same high response rates in patients with high risk as it does in lower-risk patients. "Patients with high-risk disease have underlying risk factors that makes myeloma difficult to treat, and it is encouraging to see that bortezomib may be particularly useful in these patients early in the disease course," says Dr. Dispenzieri.

While these clinical trials are helping to improve survival and quality of life, Dr. Rajkumar expects that the future of multiple myeloma treatment will be even brighter. "As our understanding of the disease increases, we expect that newer treatment options will become increasingly available," he says.

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These studies included collaborating researchers from the Mayo Clinic Cancer Center sites in Arizona, Florida and Minnesota. Other collaborators on some research are from Cleveland Clinic, Ohio; Dana Farber Cancer Institute, Boston, Mass.; Frankston Hospital, Frankston, Australia; Hospital Clinic, Barcelona, Spain; Kiev Institution of Oncology of the UAMS, Kiev, Ukraine; Medical Academy of Warsaw, Poland; the University of Wisconsin, Madison; St. Vincent"s Comprehensive Cancer Center, New York; and Celgene Corporation, Summit, N.J.

For more information on hematology research at Mayo Clinic, visit http://cancercenter.mayo.edu/mayo/research/hematologic_malignancies, and to find out about treatment options, see http://www.mayoclinic.org/.

Contact: Elizabeth Zimmermann
Mayo Clinic

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