When should myeloma cytogenetic testing be done?

Genetic testing is a powerful tool that looks at your chromosomes, the carriers of your genetic blueprint, to spot any abnormalities. But when is the right time to run these tests?

In this lesson, we'll break down exactly when genetic testing should be done in multiple myeloma and why timing matters for your diagnosis and treatment.

When should cytogenetic testing be done on the myeloma cells?

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 any time 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 an 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 a 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 the patient that has relapsed.

Doctor Rodriguez is describing a process known as clonal evolution. HealthTree University has a video explaining this concept in more detail. You can find it in our Myeloma Processes and Biological Events course, located in the Myeloma Genetics/Genomics module.

If someone is diagnosed with high-risk myeloma, a diagnosis, does genetic testing need to be redone at relapse?

For somebody who is high risk right out of the gate, for whom you're not considering any sort of targeted type therapy, it may not actually be as important to repeat molecular profiling in a patient you already know is high risk. But in a patient who wasn't in the past, it is helpful to understand if they have acquired high risk features that might affect the way that you approach their next line of therapy, particularly the maintenance part of it.

Some abnormalities, like the 11;14 translocation that's present in 15% of patients or so at diagnosis, and it's kind of unusual to acquire it later. It's it's an initiating mutation. It's not something that you pick up along the way, it could theoretically be something that you lose along the way if another clone becomes dominant.

And so again, I just want to stress that for choosing a targeted therapy based on a target that was identified on a bone marrow biopsy five years ago, seven years ago, that's not there, there would not be recommended.

It is very usual to repeat a bone marrow biopsy and make sure at that time that the target you're looking, you know, that you're planning to go after on those myeloma cells is still present.

I would contend that if you're intending to go for cure in somebody, that all patients upfront that are going to be intensively treated, they're not expensive tests. It pales into insignificance in comparison to the therapies that we use and the information about the subtype of disease and the risk assessment is invaluable.

And so definitely at upfront when you relapse, it's going to be different. I could make a strong case to look at relapse. And each relapse, I'd like to make an argument that in the future you might do if you're not in a complete response and you can measure some disease, that it might be important to know that information because you could treat the disease with a targeted treatment.

So we might see the way we approach the management of myeloma, long term change over time. And as we're able to use circulating DNA from the tumor taken from the blood, it may become increasingly possible to do that because no patient wants to have exactly regular bone marrow, that is for sure.

Can you do genetic testing? When you are in a remission?

You need either be newly diagnosed or you need to be in relapse. Because the genetic testing is not just done on cells in your body. The genetic testing is done on the myeloma cells.

So what we do for the genetic testing, for instance, when you're newly diagnosed, we take out bone marrow, we aspirate cells. And when we aspirate cells it's a mixture of normal cells of your blood forming system of your hematopoietic system mixed with multiple myeloma cells.

So what we do first is we extract the multiple myeloma cells and do genetic testing on the myeloma cells. So you can imagine if you are in complete remission, it doesn't make sense if you don't have any myeloma cells in your bone marrow to do genetic testing on this.

So it only makes sense if we do genetic testing. For instance, FISH or karyotyping in patients who are newly diagnosed with a tumor bone, or when you have a relapse and you have a certain number of multiple myeloma cells in your bone marrow, which we can use to apply for the testing.

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