Using multiparameter flow cytometry and next generation sequencing to evaluate MRD in NDMM patients from the FORTE trial

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Published: 17 Dec 2019
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Dr Francesca Gay - University of Torino, Torino, Italy

Dr Francesca Gay speaks to ecancer at the 2019 ASH meeting in Orlando about the use of multiparametric flow cytometry (MDC) and next generation sequencing (NGS) to characterise complete remission (CR) in patients with newly diagnosed multiple myeloma (NDMM) in the FORTE trial.

Dr Gay explains that these techniques displayed good concordance, as the rate of patients who achieve minimal residual disease (MRD) negativity were comparable between each arm. More specifically an 80 percent agreement was seen between each test.

She describes that these tests are extremely sensitive are in line with the current definition of MRD negativity and states the main advantages of each technique.

ecancer's filming has been kindly supported by Amgen through the ecancer Global Foundation. ecancer is editorially independent and there is no influence over content


Using multiparameter flow cytometry and next generation sequencing to evaluate MRD in patients with NDMM in the FORTE trial

Dr Francesca Gay - University of Torino, Torino, Italy

The study is a study for newly diagnosed myeloma patients that are treated up front with carfilzomib, lenalidomide, dexamethasone plus transplant or carfilzomib, lenalidomide, dexamethasone without transplant or carfilzomib, cyclophosphamide and dexamethasone plus transplant. We collected the pre-maintenance MRD data of these patients and we performed multiparameter flow cytometry that had sensitivity to 10-5 and we also performed next generation sequencing. These analyses were performed at the pre-maintenance time-point.

We compared the data of patients in CR by comparing the data of the multiparameter flow cytometry with the next generation sequencing and we saw that the rate of patients who get into MRD negativity at a cut-off of 10-5, both with flow and NGS, was comparable within each arm which is a sign of good concordance between the two studies. Also analysing the concordance between 300 samples we saw that there was an 86% agreement in the results of the test.
We were also able to compare flow data, next generation flow cytometry, with a sensitivity of 10-6, with next generation sequencing, again with a sensitivity of 10-6, and again we saw good concordance with around 80% of agreement.

How sensitive were the tests?

It’s very sensitive because the current definition of MRD negativity according to the IMWG criteria is 10-5 so it’s quite sensitive. There are data that show that 10-6 is even more important from a prognostic point of view compared with 10-5. 

Have you measured in the impact of these tests on patient outcomes?

Not yet because the follow-up of the study is still short so at present we are not able to show data on survival since the follow-up is short. But we know that achieving MRD negativity strongly impacts on survival with patients achieving MRD negative disease having a prolonged survival.

What are the advantages of these tests?

Each test has advantages and disadvantages. For example, flow you can get the results more easier, more faster, but it needs a fresh sample whilst NGS needs a frozen sample. So it’s a bit longer. It doesn’t need a frozen sample but generally is done on DNA so you have to extract the DNA, you can do it even on frozen samples. So this can be in some ways an advantage, in some cases an advantage. In some others maybe you don’t get the results immediately so it’s the drawback.