LLM 2021 | Myeloma & precursor disorders: what does NGS reveal?

My talk was mainly outlining the progress that happened by genomic studies using the next-generation sequencing technology in the field of smoldering myeloma, as well as multiple myeloma, and mechanisms of resistance and relapse to myeloma therapy. In the smoldering part I highlighted the work done by us here and in Dana-Farber Cancer Institute and other centers where we sequenced the largest data sets of smoldering myeloma patients. And what we’ve seen is that some genetic biomarkers can predict the risk of progression in patients regardless of their clinical risk score. And this was something new to us. And it was also shown by other studies done by two or three other groups, one from Arkansas and the other from Mayo Clinic, showing similar data and similar results that there were some genetic biomarkers, especially, make genetic alterations, KRS oncogene, TP53 mutations or deletions and others as well that were high-risk genetic features in all of these studies or of in some of them.

I also highlighted the work by us here that is currently still in [inaudible]press where we tried even to model the heterogeneity and complexity of smoldering multiple myeloma patients to identify molecular subtypes and that there are certain molecular subtypes that could be very predictive in progression to active myeloma that requires treatment. And at the same time we did the validation of our findings in two external cohorts as well. This was for the smoldering part. For the myeloma and resistance/relapses, I highlighted some studies by different groups in the myeloma field. One of them was by the group led by Sarah Gooding at Oxford, where they identified certain mutations in the cereblon gene where it could be found in 20 to 30% of patients who are resistant to lenalidomide and pomalidomide. And other things that we highlighted in the talk was work by a group at Emory University, where they reported B-cell signature or signature that is similar to B-cells in lymphomas that could be very predictive to response to venetoclax.

Also, some work by different groups regarding response and resistance to CAR-T therapy, the BCMA CAR-T therapy. All of these findings gives us an important indication that the next-generation sequencing is important to first identify mechanisms of resistance or relapse and to molecular early characterize multiple myeloma instead of just a clinical classification and at the same time in the near future. And even from now, maybe it’s time to start having it implemented in clinical settings till it’s of course proven to be in perspective studies to be a significant feature in our patients management. And then it can be applied everywhere.