Recent advances in multiple myeloma treatment have led to improvements in survival, but the success has not been uniform. Some patients enjoy many years in clinical remission; others relapse or die within 2 years. Why do some patients do poorly? The MMRF Answer Fund hopes to answer this critical question. The Answer Fund , a 3 year, $5M effort, supports clinical research that uses genetic and clinical data collected from myeloma patients in the groundbreaking MMRF CoMMpass study to gain a better understanding of the drivers of high-risk myeloma—that is, patients who do not enjoy long-term clinical remission – and determine the most effective treatments for these patients.
One of the projects that the Answer Fund has supported is the research of Dr. Lawrence Boise, Dr. Benjamin Barwick, and their colleagues at the Winship Cancer Institute at Emory University in Atlanta, Georgia. This work was recently published in the journal Nature Communications and was co-authored by MMRF CSO Dr. Daniel Auclair. The team analyzed genetic samples from 826 newly diagnosed myeloma patients from the CoMMpass study to identify any genetic factors that contribute to poor outcomes.
Based on this research, a new, distinct translocation was identified in about 10% of patients, which was found to be associated with poor survival. This finding is significant, because this specific translocation—called IgL—tends to occur in hyperdiploid patients (which means that their myeloma cells have more chromosomes than normal cells), a group that is not normally considered high risk. As revealed by this new finding, even hyperdiploid patients with the IgL translocation represent a high-risk group.
Currently, testing for the IgL translocation is not part of routine clinical evaluation, but this test may soon be developed and available in light of these newly published findings. The ability to identify patients with an IgL translocation is even more important, because the team at Winship also showed that these patients do not benefit from treatment with immunomodulatory drugs (such as Revlimid). Therefore, this new test would not only identify patients as high risk but may also inform their treatment options.
Ultimately, these observations would not have been possible if not for the data collected from the large-scale CoMMpass Study and the MMRF’s investment into research efforts that are utilizing CoMMpass Study data to learn more about high risk myeloma. These results open the door to the possibility of using the IgL translocation as a marker of high-risk disease and poor prognosis. Research is ongoing into strategies for more quickly identifying patients with this abnormality and for identifying treatments that these patients are more likely to respond to.