Tissue Banking
Dr. Munshi. I think that’s a very important and interesting question. Some mechanisms should be developed so we could not only bank, but also study these genomic patterns. From the VA point of view, there would be some peculiarities that we should understand. One is the age of the patient population—veterans usually end up being older. Number 2, we know the disease is more common in the African American population, and we need to understand why. Tissue banking may help us compare the genomic differences and similarities to understand who may be predisposed to increased frequency of myeloma.
Finally, we still have to keep Agent Orange in mind. Although it is becoming quite an old exposure, a lot of times myeloma occurs. There is a recent paper in JAMA Oncology that showed that incidence of MGUS [monoclonal gammopathy of undetermined significance] is higher in people who are exposed to Agent Orange. Tissue banking to understand that also would be extremely important, and the banked tissue should be processed to understand what’s happening at the molecular level.
Dr. Ascensão . What’s interesting is that there are some DoD specimens (most of it is serology is my understanding), but we may be able to get other material. Having predisease tissue and watching as the patient develops MGUS, smoldering MM, or MM would allow us to see whether there were already mutational changes in the individual even before Agent Orange exposure or, perhaps, was a result of the exposure.
Dr. Mehta. If we could do that, we could even develop protocols to prevent progression of disease. We could imagine a day when we can see the first event occurring and do something to prevent the progression to MGUS and then to smoldering and overt myeloma. Now, we’re in a particularly good position having a national network to propose this type of national bank.
Dr. Ascensão. We have some advantages as a group with a high prevalence of African American patients, as Dr. Munshi mentioned. And we have the biologic components of pathogenesis with Agent Orange. I think it’s something we can afford. Dr. Roodman, what do people in the field need to know about the biology of myeloma that’s going to help them?
Dr. Roodman. People still don’t understand some of the mechanisms underlying support of myeloma growth by the microenvironment. There are multiple targets that have been examined, and none of them work especially well except for what we already use, proteasome antagonists and immunomodulatory agents. In terms of the biology of myeloma bone disease, healing myeloma bone lesions is still a major issue that needs to be addressed. The question is how to do that. I have a VA grant to look at that question and other groups are actively studying the problem.
How particular myeloma clones become dominant is still a wide-open question. Some researchers are pursuing how the microenvironment selectively allows more aggressive clones to become dominant. Currently, the major research focus is on intrinsic changes in the myeloma cell but the microenvironment may also be contributing to the process.