What chromosomal abnormalities are considered high-risk, standard risk?

[Music] how is high-risk myeloma defined so high-risk multiple myeloma has there's two different definitions or two different concepts based on who's establishing that criteria so there's the imwg criteria that establishes a high-risk multiple myelomas having 17p deletion as a part of a mutation a translocation 414 or translocation 1416 by fish studies and then there's the m smart criteria that's established by the my mayo clinic that encompasses it's a little bit more broad and in terms of genetic mutations that establish high-risk disease it would include the translocation 414 translocation 1416 the translocation 1420 it also includes 17p deletion 1q gain p53 mutation but in addition to the genetic mutations it also includes if you're a stage 3 myeloma if your gene expression profiling is of high risk signature or if you have a high high plasma cell c phase which means that if you if somebody takes a sample of your bone marrow and looks at it in the microscope and looks at the myeloma cells they try to see how many of those cells are in the s phase of the reproduction of the cells and can gauge how quickly they're reproducing so if any of the any of these things are seen in a patient they're considered a high risk if you have two of these factors it's considered a double hit if you have three of these criteria it's considered a triple hit so we often and i get into this debate with some of my colleagues about defining high-risk disease i had i had a very good debate with a colleague who said you know brian even though you have better genetic characteristics high-risk disease was high-risk disease 10 years ago it's the same high-risk disease today it's still high risk and my argument against that was it's only high risk because you haven't found the right drug to treat that particular population of cells as an example 15 or 20 years ago if a patient had a deletion of chromosome 13 it was considered a very high risk marker that is there tended to be poorer outcome in people that had that genetic characteristics of having either a portion or an entire missing chromosome 13. when the proteasome inhibitors came along velcade carphylsamide exacemib all of those pro proteasome inhibitors ended up being reasonably effective even in the patients with chromosome 13 deletion so the chromosome 13 deletion as a definition of high risk disease was only high risk prior to the advent of proteosome inhibitors that now were pretty effective in treating those high-risk diseases so now as we continue to start analyzing markers of high risk disease i think that some of the new therapies that are going to come along and that are currently being tested are going to start chipping away they're going to say you know that genetic characteristic was high risk but now this particular drug is now reasonably effective in treating that and the ultimate goal would be to chip away at high risk so that all of the high risk now becomes standard risk and all the standard risks starts becoming low risk and treatable [Music]