Risk-Based Therapy

Researchers at the Myeloma Institute for Research and Therapy have developed analytical methods and tools for identifying patients whose myeloma cells have characteristics consistent with high risk for early disease-related death. Based on a study of more than 500 newly diagnosed patients treated for multiple myeloma at the Myeloma Institute, our researchers found that measuring the activities of just 17 genes (out of the 25,000 genes in a human cell) revealed whether a patient had this high-risk form of myeloma.* Gene array analysis is now used to examine the expression levels of those 17 genes for each of our patients, providing a powerful predictor of response to therapy.

Analysis of the results from the Total Therapy 3 clinical trial revealed that separating patients according to the molecular signature for low- or high-risk myeloma revealed very different outcomes for the two groups. For patients with low-risk myeloma, survival and duration of complete response were very good, but patients with high-risk myeloma did not fare nearly as well.

These results clearly indicate that no single approach to treatment is appropriate for all patients with myeloma —a personalized approach will lead to better outcomes. This provided the impetus for incorporating molecular risk-based therapy into the next generation of Total Therapy clinical trials. 

Owen Stephens Sarah Johnson, PhD

Owen Stephens and
Sarah Johnson, PhD

Total Therapy 4 and Total Therapy 5, which began in 2008, were the first clinical trials ever to use this state-of-the-art molecular tool for personalized treatment of myeloma.  Total Therapy 4 is designed for patients with low-risk disease.  For those patients with high-risk myeloma, representing an estimated 15-20% of patients, Total Therapy 5 aims to provide results with more frequent but lower doses of chemotherapy (dose-dense vs. dose- intense) to eradicate the high-risk myeloma and prevent relapse.

A similar clinical trial, Total Therapy 6, is targeted toward patients who who have already undergone previous therapy but have not been transplanted.  Again, the dose-dense approach is employed, with early results showing the method to be highly effective in low-risk patients.

*Complete findings are reported in a plenary paper published in Blood (2007 Mar 15;109(6):2276-84).