乌鸦传媒

At December's American Society of Hematology (ASH) virtual meeting, researchers presented a study that used next-generation sequencing to in patients with multiple myeloma (MM) and cytopenias.

In this exclusive 乌鸦传媒 video, , of Moffitt Cancer Center in Tampa, Florida, talks about the findings and how genomic sequencing can play an important role in early identification of myelodysplastic syndrome (MDS).

Following is a transcript of his remarks:

What we did is we looked at a group of patients, we screened about 6,000 within our database that had a next-generation sequencing done, and identified approximately 200 -- really 196 patients -- with myeloma who met the criteria of having myeloma, having mutations that were consistent with MDS, as well as a diagnosis of MDS and cytopenias. And really what we ended up showing is that we found really four groups of individuals: patients who still had evidence of myeloma and MDS; individuals who had just MDS and no residual myeloma; those that really had neither myeloma or MDS by evidence, by pathology; [and those that have both]. And so what we looked at is, what are the molecular characteristics of these different groups?

And essentially what we found is that, those that have both diseases left over had a lot, a greater number of mutations. And then as you step down to each one, the mutation burden decreased. We also know that the greatest group there was also those who had persistent myeloma and MDS. Again, these aren't all myeloma patients, these are just patients that had all three of these category categorizations. We do know that certain mutations we found to be the highest and in these two groups, one was called ASXL1, DNMT3A, KRAS, and SF3B1, and they were the ones that were highest in that dual group. And we also know that, interestingly, different computational profiles showed up in patients with just the MDS component in RUNX1 was the mutation that seemed to be most prevalent. That again demonstrated that even in the context of MDS or clonal hematopoiesis, really what we're seeing is differential evolutionary patterns out of this context of myeloma therapy.

I think this is really important because we want to think about what is really going on. And we know that second primary malignancies are critical concerns for ours in the context of high-dose therapy, meaning high dose melphalan autologous STEM cell transplant. And how do these preexisting MDS clones versus developing clones really contribute to the long-term outcomes for our patients. And so I really think this is a step in the beginning.

We also know that also at ASH this year, there was an abstract published looking at the induced changes in mutational burden in myeloma patients treated on the IFM DFCI trial, that showed that those who got high dose melphalan had a marked increase in mutational burden, not talking about MDS just mutational burden, versus those that didn't get transplanted. So again, those are things we have to all put in context is how are these mutational burdens, how's the clonal evolution taking place, and how it may affect the long-term outcome of our patients. And maybe, and importantly, how we may want to think about treating our patients if can put all these ideas together. Are there preexisting clonal hematopoietic decisions we might want to think about when it comes to making a decision about transplant versus not, or clinical decision X versus Y.

So I think these are critical insights for us to really think about the pathology of our disease and why it's so important for clinicians and hematopathologists, to continue to work together and identify what's going on, both for the patient and inside the patient in the context of their therapy. So I think it was an exciting kind of collaborative effort, and I think taking the context of where we are in myeloma clinically, and what we know, it's really important to keep moving in the forward direction in how we may apply this to our clinical decisions.

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