A recent study in the April issue of Blood compared combination treatment regimens for elderly myeloma patients.

The study found that elderly multiple myeloma patients undergoing treatment with melphalan ^[1] (Alkeran) and prednisone ^[2] , known as an MP regimen, enjoyed higher 1-year and overall survival rates than those undergoing treatment with thalidomide ^[3] (Thalomid) and dexamethasone ^[4] (Decadron), known as a TD regimen. The combination of thalidomide and dexamethasone resulted in greater tumor reduction, but it did not ultimately translate to better outcome, due to the high rate of fatal toxicities.

The study, based on results from an ongoing clinical trial ^[5], evaluated the efficacy of MP versus TD regimens for front-line treatment of elderly patients. The MP regimen has been a standard myeloma therapy for the last 35 years, while the TD regimen represents a newer treatment regimen. The median patient age was 72, and the study followed these patients for a median duration of nearly 2.5 years.

As expected, patients on the TD regimen responded more quickly to treatment, and they showed higher rates of complete remission and very good partial response compared to individuals treated with MP (26 percent vs. 13 percent, respectively). There was no difference in time-to-progression and progression-free-survival in the two groups.

Patients treated with TD exhibited significantly less overall survival, however, especially in individuals over age 75. For all patients, estimated overall survival at one year was 69 percent for TD, as compared to 83 percent for MP. At two years, although the survival difference between the two regimens narrowed, the MP regimen continued to produce higher survival rates than the TD regimen (70 percent vs. 61 percent, respectively).

In patients over age 75 specifically, the median overall survival in the MP regimen was 41.3 months, more than double the TD regimen’s value of 19.8 months.

Those on the TD regimen not only had a higher overall death rate, but also more non-myeloma deaths – nearly double the MP number – during the first year of treatment. Principally, these included infection and cardiovascular toxicity.

The ECOG, or Eastern Cooperative Oncology Group, test assesses how a patient’s disease is progressing by evaluating its effect on daily living, including activities and energy levels. Poor performance on the ECOG test and low serum albumin levels were both independently predictive of mortality, especially during the first 12 months.

"The increased toxicity in the elderly patients was due to high-dose dex[amethasone] and not due to thalidomide," explained study author Dr. Heinz Ludwig, Head of the Department of Medicine and Medical Oncology, as well as Director of the Myeloma Reference Center, at Wilhelminen Hospital in Vienna, Austria. Dexamethasone significantly depresses the immune system, which can raise the risk of serious, life-threatening infection, and other studies have also associated dexamethasone with lower survival rates.

Thalidomide can also cause potentially severe side effects, including blood clots and psychological disturbances, but they are usually not fatal.

Nevertheless, thalidomide, too, may have at least partially contributed to lower survival, albeit through a different mechanism. This study, corroborated by other trials, found that if patients relapsed, those previously treated with TD survived for fewer months. Thalidomide exposure seems to induce drug-resistance in some patients, and while it achieves good response rates, it may also cause a more aggressive myeloma to develop at relapse.

This study holds important implications for treating elderly myeloma patients. The researchers caution that elderly patients with poor ECOG performance and related mortality indicators should not start a regimen of TD.

“In those patients a less-aggressive approach with lower doses of dexamethasone and thalidomide or thalidomide in combination with melphalan-prednisone seems to be a more appropriate treatment strategy,” the study authors explain.

Dr. Seema Singhal, professor of medicine at Northwestern's Feinberg School of Medicine and Director of the Myeloma Program, would recommend a similarly less aggressive treatment for other elderly patients with poor performance status, even if they were under 75.

For more information, see the full article in the April issue of Blood ^[6] Journal and commentary ^[7] from Dr. Pieter Sonneveld analyzing the study findings.