[Music] what are the genetic tests that can be done on a sample of bone marrow so one of the hallmarks of myeloma that we often test is for the monoclonal protein that that's in the blood and that's a good marker for the protein that's being produced by the tumor cells in the bone marrow but of course if we're interested in defining the tumor cell by genetic definitions we actually want to go into the bone marrow and isolate the tumor cells out of the bone marrow and run it through a panel of genetic tests we can test things like unique proteins that that tumor cell may be producing we can test for dna sequences that may have variations or mutations that may be a characteristic of that myeloma we can look at the expression patterns that is the amount of rna that's being produced by the gene that's the expression and we can look at the level of expression which may be abnormal in that myeloma cell every one of these measures of protein dna rna are all characteristics of the myeloma that people are starting to associate with better treatment options if you have this mutation you may respond to this therapy in in a better way than you might an alternative therapy so the bone marrow actually is the rich source for the actual tumor cells that can be genetically tested what genetic testing should myeloma patients have done what i recommend right now when you are newly diagnosed with multiple myeloma you should make sure that your doctor is testing by a fish and by karyotyping whether you have cytogenetic abnormalities that is really important within clinical trials for instance the promised trial which testing is testing a high wrist gene signature you can participate and the studies might help you whether you're high risk but right now based on for instance the ldh the cytogenetics by fish the beta2 microglobulin the albumin your presentation whether you have anemia whether you have bone lesions we can determine whether you have high risk multiple myeloma or not and we can give the treatment accordingly what is next generation sequencing everybody talks about next generation sequencing can we do anything with mutations i just want to make sure that all our myeloma patients are relaxed about that we are currently in a phase where we collect data we collect data as much as we can but we don't really know what we do with the data as of now i do not recommend that each myeloma patient outside of an academic center and outside of a clinical trial should have genetic testing for mutations because we don't know how to approach those findings the gene sequencing is as i see currently something for patients who have for instance the third and the fourth relapse patients who exhausted very much options and the next generation sequencing might help us to find a mutation that is targetable for instance we see that patients have a bref mutation in their myeloma cells and we can steal a drug from melanoma and treat myeloma patients with that with the approach to see whether we can induce another response but i think everybody is talking about that but we are still in a collecting phase and next generation sequencing is not ready for a broader use in standard patients outside of clinical trials cytogenetics and fish are part of our normal process for stratifying risk in our myeloma patients i think more detailed genetic analysis particularly for our relapsing patients at this point in time would be best done as part of a clinical trial we can identify mutations it's not always easy to know what to do with this knowledge and we don't always have drugs that address the individual mutations that drive myeloma this is part of our ongoing research enterprise and i would urge patients to consider participating in these clinical trials that aim to usher in the molecular and molecularly targeted era in myeloma therapy how is cytogenic testing done so cytogenetics can be done using different technologies you could do carrier typing you could do banding studies you can do a fluorescent uh in-situ hybridization or what we normally call fish and you might hear this word often and when you see your doctor and another way of doing it is comparative genomic hybridization and this cytogenetic studies can be done on any type of cell that we want when we're dealing with cancer and when we're dealing with multiple myeloma we're specifically interested in learning about the cytogenetics of the cancer cells or the myeloma cells by studying the cytogenetics of the myeloma cells we can have a better understanding of what characteristics these cancer cells have are there any mutations that would make these cells more aggressive than other types of myeloma cells or other types of myeloma cancers or are there any changes or mutations translocations or alterations in the structure of this dna content of the cancer cells that might make these cancer cells more aggressive or more resistant to chemotherapy or nowadays that we're actually starting to do targeted therapy are there any mutations that these cancer cells have that we could potentially use as targets for the chemotherapy that we're going to use when should you have a bone marrow biopsy done what is a liquid biopsy when we're doing testing for multiple myeloma and what mutations it has to determine what risk they are if it's high-risk disease and more likely to come back into more aggressive or if it's standard risk we normally do a bone marrow biopsy and we do a bone marrow biopsy at the time of diagnosis so we can have an understanding as to what we're dealing with when we start treatment and we also do bone marrow biopsies at time of relapse so we can understand if there's any new mutations or if we're still dealing with the same type of myeloma cells that we were dealing with at the beginning but there are several flaws with bone marrow biopsy and that is that a bone marrow biopsy only gives us a sample of one particular area of the bone and as the name multiple myeloma says multiple myeloma is composed of many different clones of myeloma cells so not all of the cells are going to have the same type of mutations and we won't see these myeloma cells spread out evenly throughout the body or the bone marrow there's going to be apache areas of myeloma cells and some areas are going to have certain mutations or certain clones whether in other parts of the bone we could find different types of clones so a liquid biopsy has become a very appealing thing for us to use whenever we're wanting to study myeloma and the mutations that it has because a liquid biopsy gives us the ability to take a blood sample and study the dna that's actually released from the cells or shed from the cancer cells into the blood we can also study the genes and mutations that are seen in myeloma cells that have been shed from the bone marrow or that are traveling through the blood migrating to a different side in the body liquid biopsy gives us the opportunity to be able to study this content without having to do a bone marrow biopsy which is gonna i'm sure be a great thing for patients because they don't have to get stuck every time we want to do studies but at the same time it's gonna give us a more broader idea of all of the myeloma cells that are in the body not just that one specific area that we're sampling so in a nutshell i would say that liquid biopsies are a very convenient way of obtaining a nice sampling of the myeloma cells that are all over the body without having to do an invasive procedure like a bone marrow biopsy now are we there at the point where we can start using liquid biopsies for a regular uh treatment and in the clinic unfortunately we're not quite there there are still clinical trials that are ongoing that are trying to compare if the information that you obtain with the liquid biopsy is the same as the information that we obtain with the bone marrow biopsy and while the studies are suggesting that the information in terms of genetic expression and genetic mutations is very similar between both we still need to do a little bit more digging in a little bit more trials to make sure that we are having a good representation and that we might not be misleading our treatment based on the results that we're getting with the liquid biopsy so genetic testing is done as part of the myeloma evaluation when somebody is diagnosed or suspected to have multiple myeloma and is going to have a bone marrow biopsy genetic testing should be done at that time whether it be by fish or by karyotyping or by now the modern types of more extensive genetic testing and genetic profiling any of those are recommended that we do whenever we're doing a diagnosis so we can have an initial picture of what type of myeloma we're dealing with the aggressiveness and any potential things that can help us determine what we're going to be doing in the future with that disease specifically when it comes to maintenance but that's not the only time we're going to be doing genetic testing we're going to also need to do genetic testing anytime somebody has a relapse and the reason why it's important to do genetic testing at the time of relapse is because there are occasions when the myeloma comes back that we're dealing with a mutated version of the myeloma we had initially or a completely different variant of the myeloma compared to what we were dealing with before and that's where clonal evolution and subclones and tumor heterogeneity kicks in myeloma is not just one type of cell with one type of mutation where all of the cells are going to be the same in multiple myeloma we're going to have different varieties or different flavors of these cancer cells and some of these are going to have certain mutations and some of them are going to have other types of mutations that are going to make these cells either more susceptible to the chemotherapy or more aggressive so whenever we're treating somebody with multiple myeloma using chemotherapy or immunotherapy we might be selecting just a population of those cells and killing off just a portion of the myeloma and then a small remaining portion of the myeloma is the one that's going to grow so doing a bone marrow biopsy and doing cytogenetics or hopefully in the future liquid biopsies and and doing cytogenetics to know what mutations these cells have are going to help us guide us in terms of how to establish the next treatment for for the patient that has relapsed [Music]