Age No Contraindication to High-Dose Therapy in Myeloma

NEW ORLEANS —Age should not be a contraindication for high-dose therapy based on melphalan (Alkeran) in patients with multiple myeloma, according to an analysis by researchers at the Myeloma and Transplantation Research Center, University of Arkansas for Medical Sciences, Little Rock.

Bart Barlogie, MD, professor of medicine, conceded that older age groups fare worse on standard chemotherapy, but added that with the newer and more effective high-dose protocols, persons over 65 have an outcome equal to that of younger patients. Dr. Barlogie presented his findings at the 41st annual meeting of the American Society of Hematology.

Earlier analyses of five myeloma trials from the Southwest Oncology Group, which included 2,150 patients with newly diagnosed multiple myeloma, found median survival to vary by age: 37 months for patients under 65 years, 30 months for those 65 to 74, and 19 months for patients over 74 (P < .001). By univariate and multivariate analyses, the adverse effect of age was confirmed in those trials.

Superior results with dose-intensified chemotherapy and peripheral blood stem cell support suggested that age as a prognostic factor should be reassessed. Dr. Barlogie and his colleagues evaluated 1,004 successive patients enrolled in tandem high-dose therapy/transplant trials at the University of Arkansas. They also conducted a pair-mate analysis of 102 patients aged 65 and older taken from this larger population.

The study found that event-free survival and overall survival were virtually identical between the two age groups when the analysis controlled for two key variables in outcome—B2 micro-globulin (B2M) level and chromosome 13 deletion status.

“There is no shred of evidence that age, as such, is an unfavorable feature for outcome in multiple myeloma,” Dr. Barlogie said.

Before adjusting for prognostic factors, event-free survival was 1.9 years in patients under 65 and 1.4 in those over 65 (P < .02). Median overall survival was 3.3 years and 2.4 years, respectively (P < .02). “But the age differences were canceled out once the biological factors of disease were considered in the multivariate analysis,” he reported.

In the low-risk group (B2M less than 4 mg/L and no deletion of chromosome 13), the 428 patients younger than 65 years and the 35 patients who were 65 or older had an identical median survival of 4.5 years.

In the intermediate-risk group (B2M greater than 4 mg/L or deletion 13), survival was also similar (median, 2.5 years) among the 352 patients under 65 and the 54 patients who were 65 or older.

Finally, in the high-risk group (B2M greater than 4 mg/L and deletion 13), median survival was 1.2 years regardless of age.

“These data provide strong support to reverse the current Medicare policy of not granting coverage for high-dose therapy/transplant for older patients, who represent at least 50% of patients afflicted with this previously rapidly fatal malignancy,” Dr. Barlogie said.

Inferior outcome was shown when patients had a prolonged duration between prior therapy and current high-dose therapy, and when a second cycle of high-dose therapy was either not given or was delayed. “One should apply optimal cytoreductive treatment (high-dose therapy) promptly to achieve and sustain minimal residual disease,” he added.