Promising findings were reported today showing that the combination of thalidomide and dexamethasone (Thal/Dex) when used as initial therapy for multiple myeloma, slowed disease progression almost two-fold compared to dexamethasone alone. Mayo Clinic’s S. Vincent Rajkumar, M.D., presented the results of the largest ever study looking at this treatment at the annual meeting of the American Society of Clinical Oncology.

The findings were the result of an international, multicenter, randomized, double-blind, placebo-controlled clinical trial. They come after years of study by Dr. Rajkumar, a hematologist/oncologist, and his colleagues, into the most effective treatments for multiple myeloma.

“We are happy to be able to report such positive results for this still incurable cancer,” said Dr. Rajkumar. “Not only have we consistently shown that Thal/Dex reduces the amount of cancer cells in the bone marrow, but now we can state that primary therapy with this combination produces superior long-term results compared to dexamethasone alone.”

An earlier Eastern Cooperative Oncology Group randomized study (http://www.jco.org/cgi/content/full/24/3/431) led by Dr. Rajkumar showed that a significantly larger proportion of patients with newly diagnosed multiple myeloma responded to the Thal/Dex combination compared to dexamethasone alone (63 percent versus 41 percent respectively). That study led to the Food and Drug Administration (FDA) granting accelerated approval two weeks ago for thalidomide use in treating newly diagnosed multiple myeloma.

In this most recent study, Dr. Rajkumar’s team found that the average time to disease progression (increase in cancerous cells) was approximately eight months for patients taking dexamethasone alone, while patients on the Thal/Dex regimen had an average progression time exceeding 17 months. “The average progression time will likely increase,” said Dr. Rajkumar, “as follow up is still under way for many patients who have not yet begun to experience disease progression.”

Of the 470 patients (235 in each treatment arm), individuals were more likely to experience adverse events with the combination therapy, experiencing serious (grade 4) adverse events 30 percent of the time compared to 23 percent with dexamethasone alone.

One of the main side effects with Thal/Dex was deep vein thrombosis/Pulmonary embolism (blood clots in the legs and lung) which occurred in 18 percent of patients receiving the combination compared to 4 percent of patients receiving dexamethasone. Other side effects that occurred more frequently with Thal/Dex compared to dexamethasone included cerebral ischemia, myocardial ischemia and peripheral neuropathy.

While overall survival rates are not significantly different between the two arms at this point, the follow-up is too short to observe disparities, and Dr. Rajkumar and his fellow researchers will continue to monitor the results of this study. Additional follow-up of this study and demonstration of improvements in overall survival are important. “The treatment of multiple myeloma is not as simple as just finding an initial therapy that works,” said Dr. Rajkumar. “We continue to work towards improvements in therapeutic options that will lessen side effects and prolong survival. At Mayo Clinic Cancer Center, while our goal is the cure, we continue to remain committed to improving all phases of treatment, including initial therapy, stem cell transplantation, maintenance therapy, and treatments for relapsed disease.”

Although multiple myeloma accounts for only 1 percent of all cancers, it is among the most difficult cancers to treat and cure. The American Cancer Society reports that this year about 16,570 new cases will be diagnosed in the United States and more than 11,000 patients will die from it. Average survival time for a patient diagnosed with multiple myeloma is about three to four years. However, the researchers feel there is considerable hope based on this and other studies of novel agents that survival time can be significantly improved.

Other investigators who contributed to this study include Mohamad Hussein, M.D., Cleveland Clinic, Ohio; John Catalano, M.B. B.S., Frankston Hospital, Australia; Wieslaw Jedrzejczak, M.D., Ph.D., Medical Academy of Warsaw, Poland; Svetlana Sirkovich, Kiev Institution of Oncology of the UAMS, Ukraine; Marta Olesnyckyj, Zhinuan Yu, Robert Knight, M.D. and Jerry Zeldis, M.D., Ph.D., Celgene Corporation, Summit, N.J.; and Joan Blade, M.D., Hospital Clinic, Barcelona, Spain. The study was funded and sponsored by Celgene Corporation.

Mayo Clinic