Early Relapse Score in Multiple Myeloma | Meral Beksac, MD | #ASH24

My name is Meral Beksac.
I'm from Istinye University, Ankara, Turkey.
I'm attending ASH and here I'm going to be presenting a couple of abstracts.
And one of the abstracts is entitled on the role of an early relapse score to predict functional high risk.
And this is a topic, which is of importance for myeloma patients. Why?
Because we know that multiple myeloma is a heterogeneous disease, and there are patients who have very good risk, as well as those who present with, what we call ultra high risk features.
And everybody is trying to find out and also find ahead of time which patients are going to be having this type of, high risk features without the disease advancing.
And there have been, earlier attempts by the European and also from colleagues from United States, they developed, scores.
But, the prediction rate for the first 12 months after stem cell transplant was looked at high and, within the European bone marrow transplantation registry, we aim to, revise this, topic.
And we developed, EBMT early relapse goal, which was published two years ago.
And this score was based on three parameters, very basic, which is very applicable worldwide, is based on the international staging system at diagnosis, and two additional features that are detected at the time of stem cell transplant prior to transplant.
And these features are performance status and also a response to the induction regimen.
Based on these, we were able to predict that within the first 12 months, there are some patients who are almost have a 50% of relapse risk versus those who have less than 5%.
So these are five categories of patients.
And this study did not include cytogenetics as in within the EBMT among 15,000 patients, not all of them had cytogenetics available to be included in the score.
To be able to overcome this hurdle, we approached the, World Bone Marrow Transplant Group and which also has data from five different registries, again, about 15,000 of patients and the majority are coming from CIBMTR also, additional registries from worldwide, including Australia, Asia, Japan and the Mediterranean region, and also some EBMT patients which were not included in the original study.
Based on this, we were able to present here in this Congress that, within the standard list and also among the high risk patients who are presenting based on their cytogenetic feature, the score is able to differentiate and recognize the same very low and also high risk patients who are going to progress within the first year after the stem cell transplant.
So we don't need to include cytogenetics into the score because the ability of the score is present for both groups.
So this is what we have found out so far.
And during this meeting, there are other groups who are trying to find out the factors that can predict functional high risk, which is the early relapse patients within the first 12 months after transplant or within 18 months from diagnosis.
These studies, one of them is a very sophisticated study looking at the genes structure from the composite study.
And they were able to see that even those patients who have standard risk features based on their gene expression, it doesn't exclude the risk of early relapse.
So I think our data has validity based on the response to induction, which is also shown in that study from the Compas data.
Response prior to the transplant being less PR was also predictive.
So I think in future we might be able to, have this approach accepted by, more authorities and to be, applicable for daily practice.
And of course, there is space to improve the score.
And that's what we are working upon.
Because those patients are the ones who are candidates for more advanced treatments.
And so that with without having the clinical features of an advanced disease before they, they have renal impairment or bone destruction, then those patients can be approached, earlier with such as CAR-T therapies or by bispecific, which are more expensive and hard to reach treatments.
And, these are the ones who are, candidate for novel treatments and not, the low dose standard maintenance approach.
And there are some now new trials which are trying to approach these patients there. There are some studies.
But their definition of a functional high-risk is not based on our score.
Maybe for future, they clinical trials may adopt our score in their inclusion criteria.
I think, regardless of their, the risk, all patients deserve the best treatment, that's for sure.
And currently, quadruplets are the best treatments.
And I think based on their additional features, such as frailty, their renal functions, their kidney functions and their social status, being able to visit the hospitals frequently.
So these are the determinants of how they can receive these quadruplets.
But it's also possible that they may start with a lower intensity of dosing.
And then as time goes by and they become more stronger and more, their, and their endurance is, stronger and more, their, and their endurance is, is more strong so that they can afford more intensive regimens.
That's the way to go, because myeloma is a heterogeneous disease, not in terms of, from, from different from one patient to the other, but within the same patient, there might be, cells who have different, features
both in biological and also, response to treatment as well.
So the way we envision the best treatment in the beginning, it's possible that we will be able to get rid of that heterogeneity, which may appear based on the less intensive regimen that we can induce refractory and resistant cells that will be become difficult to treat, later on.