Substantial Activity of Thalidomide in Multiple Myeloma, Study

An Arkansas Cancer Research Center study, published in the November 18, 1999, issue of The New England Journal of Medicine, found that thalidomide (Thalidomid) effectively reduced or, in some cases, eliminated tumor activity in multiple myeloma patients who had not responded previously to other agents.

The phase II study of 84 patients with progressive disease found that 10% enjoyed a complete or near-complete remission, and 32% experienced a reduction in serum or urine paraproteins of at least 25%. To qualify as a response, the reduction in paraproteins must have been observed minimally twice, at 6-week intervals. In addition, a majority of patients exhibited other evidence of antitumor activity, said Bart Barlogie,MD, PhD, director of the Arkansas Cancer Research Center, and the study’s principal investigator. These included a reduction in the percentage of plasma cells in bone marrow and an increase in blood hemoglobin levels.

Responses Maintained Over the Follow-up Period

According to Dr. Barlogie, responses were observed in 78% of patients within 2 months of beginning thalidomide therapy, with nearly all patients demonstrating a response within 4 months. The study included 76 patients whose disease had previously relapsed following high-dose chemotherapy. Responses to thalidomide were maintained over the 12-month follow-up period in the majority of patients.

“These findings of the activity of thalidomide in multiple myeloma have been subsequently confirmed by other investigators, further strengthening the position of thalidomide as a potential top-line therapy for myeloma patients,” said Dr. Barlogie. “In my opinion, these data place thalidomide in a class with melphalan (Alkeran) and glucocorticoids as the most promising treatment options for multiple myeloma patients.”

“Being an advocate for improved solutions for all myeloma patients and a patient myself, I am very encouraged by the study results coming out of the Arkansas Cancer Research Center,” said Kathy Giusti, president of the Multiple Myeloma Research Foundation. “To finally have evidence that there may be another weapon against this awful disease is exciting.”

Inhibition of Angiogenesis

“Thalidomide may be exerting its activity by inhibition of the angiogenesis induced by multiple myeloma,” said Dr. Barlogie. “Coupled with the fact that thalidomide doesn’t appear to cause an array of adverse effects traditionally associated with chemotherapy, the study suggests that the drug could be an ideal agent for use in combination with other chemotherapeutic regimens. We are currently investigating this hypothesis with a $13.5 million research grant from the National Institutes of Health. By understanding how thalidomide works against multiple myeloma, we hope to better understand myeloma cell behavior and thus develop novel strategies to combat and ultimately cure this disease.”

More than one-third of the study’s patients experienced some adverse effects, including constipation, weakness or fatigue, and somnolence. Reducing the dose of thalidomide alleviated these adverse effects in most patients.