Mayo Clinic researchers announce promising next generation treatments for multiple myeloma

The combination of two pills — thalidomide and dexamethasone — may be an effective alternative to the intravenous chemotherapy commonly prescribed to patients with multiple myeloma, according to a large collaborative study conducted by the Eastern Cooperative Oncology Group and led by a Mayo Clinic investigator. More than 15,000 Americans are diagnosed annually with multiple myeloma, an incurable cancer of the bone marrow.

Mayo Clinic researchers announced their findings today during a press conference at the annual meeting of the American Society of Hematology in San Diego. They also announced a second new finding: results of a smaller study using a less toxic and more effective “cousin” to thalidomide that they believe will soon assume a leading role in the treatment of myeloma.

The fact that thalidomide — an old drug with a tragic past of causing birth defects — can slow the progression of recurrent multiple myeloma is not new. But the studies discussed today show that thalidomide and its analog can be effectively combined with dexamethasone as the initial treatment for patients newly diagnosed with multiple myeloma.

“These oral regimens are as effective as the standard intravenous chemotherapy treatments commonly used as initial therapy for myeloma,” says Vincent Rajkumar, M.D., the Mayo Clinic hematologist/oncologist who led the studies. “However, the treatment of multiple myeloma is like a marathon. In addition to improving the initial therapy to get the disease under control, we need to improve other phases of treatment which include stem cell transplantation, maintenance therapy and treatment of relapse. At Mayo, we are committed to improving all phases of treatment, and at the same time, we are striving to develop a cure.”

Major findings of the two studies

In the first study, 207 patients newly diagnosed with myeloma were treated. Half were randomly assigned to the combination regimen of thalidomide and dexamethasone. The other half were assigned to take dexamethasone alone as the first treatment for their disease. After four months, a significantly greater proportion of patients — 63 percent — responded to the combination of thalidomide plus dexamethasone compared to the 41 percent whose cancer responded to dexamethasone alone.

While these results are encouraging, the side effects of thalidomide plus dexamethasone were significantly higher compared to dexamethasone alone, particularly blood clots. Blood clots occurred in about 18 percent of patients who took the combination drug regimen, compared to only 3 percent of patients who took dexamethasone alone. The researchers stated that the risks and benefits need to be weighed for each patient in determining what regimen to use for initial therapy. Researchers also recommend patients receive blood thinners to minimize the risk of blood clots when using thalidomide plus dexamethasone.

“Based on this study, thalidomide plus dexamethasone has probably become an appropriate replacement for intravenous vincristine, adriamycin, dexamethasone (VAD) chemotherapy, except for patients with less aggressive disease for whom dexamethasone alone may be adequate,” says Dr. Rajkumar.

In the second study, Mayo Clinic researchers showed that using a new “cousin” of thalidomide may be more effective and safer in treating newly diagnosed myeloma. This analog of thalidomide is called CC-5013 (lenalidomide) and is not currently commercially available.

Mayo Clinic began a small, tightly-controlled study in 30 patients who were newly diagnosed with multiple myeloma. Patients were treated with CC-5013 plus dexamethasone. The results of this study were announced for the first time at the San Diego meeting. Out of 30 patients treated, 83 percent responded to this therapy, and — in dramatic contrast to the thalidomide experience — no blood clots have been observed so far.

“This regimen appears more effective than the thalidomide-dexamethasone regimen, with fewer side effects, and may in the future replace other regimens including the thalidomide-dexamethasone combination as initial treatment for myeloma,” Dr. Rajkumar says.

The Eastern Cooperative Oncology Group has just initiated a large, multicenter trial to study CC-5013 in more than 400 newly diagnosed multiple myeloma patients.