Risk Stratification for Smoldering Myeloma | Irene Ghobrial, MD | IMS 2024

Hello, my name is Irene Gabriel. I'm from Dana-Farber Cancer Institute in Boston, Massachusetts, and I'm here to talk about risk stratification for small-drink myeloma. We know that patients with small-drink myeloma have a big decision to make. They want to know, am I going to progress very fast or am I going to be one of those patients who may not progress very fast and I have the time to enjoy and watch and wait? And the next question will be, what is my own personal risk of progressing to myeloma and then what can I do about it to intercept it or prevent it? And these are critical questions that when we're diagnosed with this, we want answers from our physicians. So the first thing is, what is the risk stratification for small-drink myeloma? We have good clinical markers that can help us understand if someone is at high risk of small-drink myeloma to progress to myeloma and some that are not. But unfortunately, they're not perfect. That means that sometimes we say that someone is low risk, but actually they're progressing very rapidly and they may end up going on to myeloma. Or we may say that someone is high risk, but they may not progress very fast. So can we improve on our risk stratification? And we have a few things that can be developed in the near future so that we can be more precise in our risk stratification. The first one is, can we use dynamic changes or evolving numbers of our M-spike and light chain? We developed a model called Pangea, which means you put the whole world back together. And that's the idea that we can indeed work together to develop a dynamic model for disease progression. Your M-spike is going up, your light chain is going up. That is already a suggestion that your cells are starting to grow and go towards myeloma. The second one is, can we use genomics and net generation sequencing instead of fish from the bone marrow? And in fact, can we use circulating tumor cells to predict for us whether someone will progress or not? And indeed, we found that you can use a minimal number of cells and do more genome sequencing and track someone if they're progressing or not and developed a new genomic model that can be very predictive in whether someone will progress to myeloma or not. Then I can add to it transcriptomics, which is like the gene expression profiling in the old days, because it can help us understand beyond your chromosomal abnormalities, beyond your translocation, am I going to progress faster or not? Are the cells cycling faster or not? Am I having gene expression data that indicates that I'm going to progress or not? And these can all be put together from a simple peripheral blood sample. So from a blood sample, I can understand what is my cytogenetic abnormality, what is my DNA changes, and what are my RNA changes that are happening. And then I can also look at the immune system also from the same blood sample, and it can tell me if my cells, my T cells are exhausted, my T cells are functional. And this can help me not only being a biomarker for prediction of progression, but also am I going to respond to therapy? Because the next question in any patient's mind is, should I be treated early? And we have a lot of options of treatment, but one of the best options we're testing right now is immunotherapy. Can I use bispecifics and can I use CAR-T as early as possible when my T cells are working well and when my cancer cells, the number and the genomics are lower? And that's the perfect time to use immunotherapy in prevention or interception of small dream myoma. So those steps are all put together when we sit down with a patient, we talk about all of that, and we start putting together their own risk prediction. And then by doing that, we can start asking the question, should I be treated and what kind of therapy should I use? Is it immunotherapy or not? Or should I continue washing weight carefully? And I know that someone will be there to tell me if my model or my risk is changing.