Last Updated: 2009-10-21 18:17:39 -0400 (Reuters Health)

NEW YORK (Reuters Health) - In patients with newly diagnosed multiple myeloma, combining the thalidomide analog lenalidomide with low-dose dexamethasone led to better short-term survival than lenalidomide plus high-dose dexamethasone, along with fewer serious side effects.

In fact, the randomized trial was stopped early, at a median follow-up of 12.5 months, because overall survival was significantly higher with low-dose than with high-dose dexamethasone (96% vs 87%, p = 0.0002).

As Dr. S. Vincent Rajkumar, from the Mayo Clinic in Rochester, Minnesota, and associates report in an online publication October 22 in The Lancet Oncology, all of the 445 patients with untreated, symptomatic myeloma took lenalidomide, 25 mg daily, on days 1-21 of a 28-day cycle. The high-dose dexamethasone group took 40 mg by mouth on days 1-4, 9-12, and 17-20 of the 28-day cycle. The low-dose group took 40 mg on days 1, 8, 15, and 22.

After 4 cycles, patients could discontinue therapy to undergo stem cell transplantation or continue until disease progression. The median duration of therapy was 4 months in the high-dose group and 6 months in the low-dose group.

After 4 cycles, the overall response rate was higher with the high-dose regimen (79% vs 68.3%, p = 0.008).

During the first 4 months, the high-dose group had significantly more grade 3 or higher adverse effects (52% vs 35%, p = 0.0001) and early mortality (5% vs 0.4%, p = 0.003).

At 12.5 months, when the study was stopped, patients in the high-dose group were crossed over to low-dose. Two-year overall survival rates were 87% and 75% in the high-dose and low-dose groups, respectively.

The investigators note that "almost all current phase 3 trials" are now using low-dose dexamethasone for combination regimens.

They point out, however, that "high-dose dexamethasone might still have a role in the treatment of patients with acute renal failure caused by myeloma cast nephropathy, cord compression from myeloma, or aggressive refractory disease."

Lancet Oncol 2009.