Thalidomide Improves Survival for Older Multiple Myeloma Patients

October 5, 2007

LILLE, France -- Older treatment-naïve stages II or III multiple myeloma patients have a survival advantage when thalidomide (Thalomid) is added to standard therapy, researchers found in a randomized trial.

LILLE, France, Oct. 5 -- Older treatment-nave stages II or III multiple myeloma patients have a survival advantage when thalidomide (Thalomid) is added to standard therapy, researchers found in a randomized trial.

Overall survival at 51.5 months with the combination of thalidomide, melphalan (Alkeran), and prednisone was 41% (18.4 months) longer than with melphalan and prednisone alone--and 31% (13.3 months) longer than with melphalan-based stem cell infusion therapy.

These findings provided a third large randomized trial to the published evidence for a survival benefit from adding thalidomide to the therapy mix, reported Thierry Facon, M.D., of Hpital Claude Huriez at the Centre Hospitalier Universitaire here, and colleagues, in the Oct. 6 issue of The Lancet.

A thalidomide-based combination should be the new standard of care for multiple myeloma in older treatment-nave patients, the researchers said.

In an accompanying editorial, Antonio Palumbo, M.D., and Mario Boccadoro, M.D., both of the Universit di Torino in Italy, agreed.

"After 50 years of unsuccessful attempts to find new and more effective treatment approaches suitable for most patients," they wrote, "we now have extensive evidence to support the introduction of melphalan and prednisone plus thalidomide as the standard of care for elderly patients with multiple myeloma."

Dr. Facon's Intergroupe Francophone du Mylome group study included 447 newly diagnosed multiple myeloma patients ages 65 to 75. They were randomized to 12 six-week cycles of 0.25 mg/kg of melphalan and 2 mg/kg of prednisone given orally for four days per cycle, the same regimen plus thalidomide given daily at a dose not exceeding 400 mg per day continuously during the 12 cycles, or autologous stem cell transplantation with two 100 mg/m doses of melphalan.

After an average 51.5 months of follow-up, median overall survival was significantly better in the thalidomide group than with melphalan and prednisone alone (51.6 versus 33.2 months, hazard ratio 0.59, P=0.0006) or with stem cell transplantation (51.6 versus 38.3 months, HR 0.69, P=0.027).

After adjustment for prognostic factors, the thalidomide combination remained best at prolonging overall survival (HR 0.49 versus the standard regimen, P=0.0002, and HR 0.56 versus stem cell transplant, P=0.006).

For progression-free survival, the thalidomide group again came out ahead of melphalan and prednisone alone (HR 0.51, P

"Although the toxic effects we observed with melphalan and prednisone plus thalidomide were acceptable," they wrote, "efforts should be made to reduce neurotoxicity, somnolence, and constipation through use of a lower thalidomide dose (100 mg or 200 mg per day) along with a shorter treatment duration, and to prevent thromboembolism with adequate prophylaxis."

Although "a new standard of care has been defined" with thalidomide for multiple myeloma, Drs. Palumbo and Boccadoro said, "the optimum dose of thalidomide, the number of cycles, and the need for maintenance therapy with single-agent thalidomide still need to be investigated."

Dr. Facon and two coauthors reported receiving scientific advisory board and lecture fees from Pharmion, Janssen Cilag, and Celgene. Drs. Palumbo and Boccadoro reported receiving scientific advisory board and lecture fees from Pharmion and Celgene.

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