Advanced Myeloma Patients Respond to Proteasome Inhibitor

December 11, 2002

Jane Salodof MacNeil

Dec. 11, 2002 (Philadelphia) — Bortezomib (Velcade), an experimental drug formerly known as PS-341, stabilized or improved the condition of more than a third of patients with advanced multiple myeloma in a phase II clinical trial.

All 202 patients in the multicenter study had failed at least two other therapies, including thalidomide and bone marrow transplants. Ten percent had a complete response to bortezomib, the first in a new class of anticancer agents called proteasome inhibitors.

The median survival for the study group of relapsed and refractory patients was 16 months, with patients still showing a response to bortezomib a year after treatment. The median time to progression was seven months.

Paul Richardson, MD, from the Dana Farber Cancer Center in Boston, Massachusetts, presented the data here at the American Society of Hematology annual meeting.

The overall response rate was 35%, and 27% had major responses. The data, which were updated from an earlier report in the abstract book, covered 193 patients who could be evaluated.

A phase III trial is already underway for the agent, Dr. Richardson said. It is being developed by Millennium Pharmaceuticals Inc. (Cambridge, Massachusetts), which supported the research.

Bortezomib was administered by intravenous injection at a dose of 1.3 mg/m 2 twice a week for two weeks followed by a week of rest. The maximum number of cycles evaluated in the trial was eight, but patients were allowed to continue if a benefit was seen.

Dexamethasone was also permitted for patients who had progressive disease after two cycles or stable disease after four cycles. Dr. Richardson reported that 39% of patients were given dexamethasone, and 17% of them improved.

The most common adverse effects were gastrointestinal, he said. Twelve percent of patients had a dose reduction because of peripheral neuropathy, and 4% discontinued because it, Dr. Richardson reported. Because all patients had been through rigorous treatments before entering the trial, he suggested that some might have been suffering from the condition before starting on bortezomib. Nine of 10 patients had been refractory to their last treatment, and 61% had undergone transplantation.

Bortezomib was one of several novel agents reported on at the conference by Dr. Richardson and colleagues from the Dana Farber laboratory of principal investigator Kenneth C. Anderson, MD. In an earlier session, Dr. Anderson had singled out bortezomib and revimid, a drug from the same family as thalidomide, as the most promising.

Both are able to overcome drug resistance, he said, describing revimid as a more potent, less toxic form of thalidomide. "I hope they are going to get used together," Dr. Anderson said, predicting the drugs would be most effective by working side by side but on different targets.

Although transplantation remains the standard treatment for multiple myeloma, transplant specialist Jean-Luc Harousseau of the University of Nantes in France told Medscape that his field needs novel agents for what is still an incurable disease. "With the drugs we have currently, it's not possible to improve the results, he said. "The future of the treatment of myeloma will be the use of all these agents in combination. What is exciting is the expectation that Velcade can be active in patients with poor prognosis."

ASH 44th Annual Meeting: Abstract 385. Presented Dec. 9, 2002.

Reviewed by Gary D. Vogin, MD

Jane Salodof MacNeil is a freelance writer for Medscape.

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