Drug Combination Effective Against Multiple Myeloma

Combining a new thalidomide derivative with a steroid slows progress of multiple myeloma, an incurable bone marrow cancer, and prolongs the lives of patients who have relapsed from previous treatment, researchers reported in the November 22 issue of the New England Journal of Medicine.

The study, conducted at 44 centers in the United States and Canada, was led by The University of Texas M. D. Anderson Cancer Center. In Milwaukee, Medical College of Wisconsin bone marrow transplant researchers entered 12 myeloma patients in the study at Froedtert Hospital. Patients received either a combination of lenalidomide (Revlimid™) and the steroid dexamethasone, or a placebo with the steroid.

In the final analysis, patients taking the lenalidomide combination had a longer survival, on average nine months more than patients receiving a placebo. The results for patients on lenalidomide were impressive enough that in December 2005, the trial was halted early so that those on placebo could be switched over to the active drug, lenalidomide.

The research by North American Multiple Myeloma Study investigators, and a parallel international trial which reported similar findings, led to the approval of lenalidomide for myeloma by the US Food and Drug Administration (FDA) in 2006.

"By undertaking this major collaboration, myeloma investigators have been able to expedite results and bring about better treatment options to the market for patients with this disease," said Parameswaran Hari, MD, Assistant Professor of Medicine and a myeloma specialist at the Medical College, who led the Milwaukee arm of the study. "The new combination of drugs offers physicians a major addition to our drug armamentarium to treat myeloma."

Multiple myeloma is caused by the abnormal growth of plasma cells, a type of white blood cell, in the bone marrow. These cells multiply rapidly, crowding out normal red and white blood cells and platelets. Tumors starting in the bone marrow may cause pain, and weaken bones, predisposing them to fracture. In the United States, about 16,000 people are diagnosed with multiple myeloma annually, and about 11,000 succumb to the disease each year.

Thalidomide, originally marketed for morning sickness, had to be withdrawn after it was shown to cause fetal malformations in pregnant women. However, in 1998, it was identified as a breakthrough drug for patients with multiple myeloma. Celgene Corporation, which markets thalidomide (Thalomid™), designed Lenalidomide also. The company chemically altered thalidomide to make lenalidomide, known commercially as Revlimid™, in hopes of reducing side effects and improving its effectiveness against myeloma. Both drugs attack both the malignant plasma 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 group. Currently, lenalidomide is being tested as a front-line therapy and in combination with other medications in a variety of clinical trials.

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 adjusting 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 research was funded by Celgene. Dr. Hari has received grant funds and lecture fees from Celgene. This relationship is handled in accordance with the Medical College's conflict of interest policies.

Other key institutions that participated in the study were: Princess Margaret Hospital in Toronto; Weill Cornell Medical College; Cross Cancer Institute, Edmonton, Alberta; University of Pennsylvania Cancer Center; The Cancer Center at Hackensack University Medical Center; Johns Hopkins; Mayo Clinic Cancer Center; Roswell Park Cancer Institute; and Emory University.

MCW Health News presents up-to-date information on patient care and medical research by the physicians of the Medical College of Wisconsin.