MDS updates from iwMDS-iwMPN 2024 | Updates in the diagnosis, classification & risk stratification of MDS

Maria Teresa Voso:

I’m Maria Teresa Voso. I am Professor of hematology at Tor Vergata University in Rome, Italy. And today, I am here at the iwMDS meeting in Boston, and I would like to introduce to you some very important MDS experts from US. Please?

Chris Hourigan:

My name is Dr. Chris Hourigan. I’m from Virginia Tech Fralin Biomedical Research Institute in Washington, DC.

Robert Hasserjian:

I’m Robert Hasserjian. I’m a hematopathologist at Mass General Hospital in Boston – right here in Boston.

Somedeb Ball:

Hi, I’m Somedeb Ball, Assistant Professor of medicine from Vanderbilt University at Nashville, Tennessee.

Maria Teresa Voso:

Yes. Today, we talked a lot about classifications and also diagnosis of MDS. So, I would like Robert to start a little bit with some guidelines on updated MDS diagnosis.

Robert Hasserjian:

Yeah, so I spoke about efforts I’ve been doing with hematopathology colleagues and other members of the International Consortium about developing guidelines for how we accurately can diagnose and provide information to MDS in the reports. If your diagnosis is now correct, then the patient may now be managed correctly, and the clinical trials will be done on the correct data. So, it’s very important we get the diagnosis right at the beginning, so that’s why we feel it’s important.

So, we put out several guidelines involved that could help pathologists, interpret the morphology, interpret the classification. And now, we have two classifications that complicate things and include the relevant data in their report so that the clinician can be fully informed to provide prognosis to the patient.

And if that data is used in trials, that data will be correct and will be robust, and the trial will be based on data that’s accurate. So, we think that’s very important to start with the right diagnosis before we proceeding with treatment instead in these patients.

Maria Teresa Voso:

Thank you. And you mentioned we have had the publication in 2022 of two different myeloid neoplasm classifications, the WHO and the ICC, and of course, there is a need for harmonization. Somedeb, you presented a project on the harmonization of the two classifications and using really large database. Can you comment on that?

Somedeb Ball:

Yeah, sure. Following up to what Dr. Hasserjian said, our project really aimed at harmonizing the two diverging classification systems that have come up in recent years, as you mentioned. For patients with MDS, that has created a lot of confusion in clinical care as well as communication with patients and families and within our colleagues as well, and also created obstacles to some clinical trial design and trial protocol for these patients.

So, we wanted to put together a large number of patients, trans-Atlantic from US and Europe, on the International Consortium for MDS where we have looked at 7,000 patients of MDS and 1,000 of AML trying to really go into the details of different classification systems subgroups.

Our goal was not to come up with a third classification, but to rather try to find what makes sense biologically in terms of defining different classification subgroups to hopefully aid our pathologists and give us the right diagnosis for our patients so that we can choose the best therapy for them going forward to improve the overall outcomes.

Maria Teresa Voso:

Yeah. And indeed, one of the greatest changes has been this introduction of this new MDS/AML category, which lowered the blast count to 10% and introduced this new category with some molecular changes, which are similar to AML, myelodysplasia-related, but of course we cannot translate the results in myelodysplasia-related or even the classification systems for AML, myelodysplasia-related to MDS/AML. So, that is another issue that is waiting for some adjustment and also some new prognostication system and also trials including these types of patients.

One of the issues that we also have is MRD assessment in MDS possible, in the context of transplant and out of that context?

Chris Hourigan:

Yeah, so I think it’s important just to restate that allogeneic transplant is the only curative therapy we have. And so, we can make an appropriate diagnosis, we can put someone in a prognostic risk group for therapy. But really, the only curative therapy we have is transplant. And so, I was asked to think about how we could identify those patients for whom that transplant therapy may fail, who they may have disease progression of recurrence.

I think the challenge is a harder one than has been the case in acute myeloid leukemia where it makes a lot of sense to talk about measurable residual disease, where we’re talking about often some component of normal hematopoiesis, and then a malignant clone. Tracking features of that malignant clone during the points of therapy is strongly associated with relapse risk and overall survival.

In MDS, we’re in a different situation, we have a field effect, and we’re not just dealing with malignant transformation as the only potential form of disease progression. And so, I talked about the fact we don’t offer transplant to many patients with MDS for a variety of reasons, but for those small population of patients who do receive an allogeneic transplant for that fraction of those who will relapse, how could we think about predictive markers?

And what we see then when we’re really coming down to individual patient-level predictions that some of these prognostic scaling scores will let us down. And so, there is a need to develop more specific markers. The evidence base in rare diseases, and rare complications of rare treatments of rare diseases is tough, and it really requires consortium as this iwMDS group is.

Maria Teresa Voso:

Yes, I think so. We have solved a lot of questions in MDS, newer classification, newer prognostication. Hopefully, new treatments. Not many new treatments in high-risk MDS, but that’s what the International Working Group on MDS is for, so we hopefully will solve more questions in the next years.