Tools for Risk Stratification and Prognosis in MDS

EP: 1.MDS: Typical Patient Presentation, Diagnostic Process, and Evolving Terminology

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EP: 2.Tools for Risk Stratification and Prognosis in MDS

EP: 3.Considerations for MDS Pathology and Risk Status Reporting

EP: 4.First-Line Treatment Options for Lower-Risk MDS

EP: 5.Second-Line Treatment Options for Lower-Risk MDS

EP: 6.Case 1 Presentation: Lower-Risk MDS with Multiple Chromosomal Abnormalities

EP: 7.Case 1: Expert Panelist Commentary

EP: 8.The Impact of p53 Mutations and 5q Deletions on Lower-Risk MDS Treatment Response

EP: 9.Case 2 Presentation: Lower-Risk MDS-RS With an SF3B1 Mutation

EP: 10.Case 2 Discussion and Considerations for Second-Line Treatment Selection

EP: 11.MEDALIST Trial Updates: ASH 2022 and EHA 2022

EP: 12.Additional Updates in Second-Line Treatment of Lower-Risk MDS

EP: 13.Higher-Risk MDS: First- and Second-Line Therapies and Case 3 Presentation/Discussion

EP: 14.Recent Data Updates in Higher-Risk MDS

EP: 15.MDS/MPN-RS-T Overlap Syndromes

EP: 16.Summary of Unmet Needs and Future Directions in MDS

Transcript:

Rami Komrokji, MD: Once we diagnose, the next step is we always try to get an estimate of the disease outcome, prognosis, or what we call risk stratification. Uwe, we’ll ask you to bring us up to speed, update us, there are a lot of evolving prognostic systems there. How do you look at that, and what do you use in your practice?

Uwe Platzbecker, MD: Risk stratification, as you mentioned before, is the next step after you make the work-up with regard to the morphology, blast count is important, blood counts, genetics, including molecular abnormalities. We’ve had an evolution of prognostication tools in the last 10 years, I would say. There were also some tools that appeared and disappeared. But I think the recent development is the IPSS-M [International Prognostic Scoring System-Molecular], the molecular-based IPSS, which I think is a very sophisticated tool, but has some requirements.

This is that you do the entire molecular work-up on a patient. Although the tool also allows some missing variables, and you can still do the prognostication. But I think, at least in Germany and in the European Union, the majority of the drugs we are using are approved based on IPSS still. Azacitidine is approved on the IPSS, EPO [erythropoietin] is also approved based on the IPSS. And the IPSS-R [International Prognostic Scoring System-Revised] was the driver to approve luspatercept, as we know. I think the IPSS-M is a very advanced tool to do prognostication, especially for me, in younger patients, where, let’s say, there are cytopenias but they are not affecting quality of life, but a mix of molecular abnormalities, and a slightly elevated blast count in the bone marrow, and then you have to make a decision. Also, when counseling such a patient, you have to determine what is the optimal timing of transplant in this patient? I think, for these patients, IPSS-M is optimal.

For the vast majority of patients above the age of 70, it’s always good to have this tool in hand when you counsel them, and you basically talk about potential interventions and treatments. But the IPSS-M, I think, cannot help you to select a given treatment. Because it’s prognostic, yes, but I think we only have a couple of agents in our hands outside of clinical trials. I think that’s still the limitation, having these wonderful tools in our hand, but we only have a handful of therapeutic options that we can apply to these patients.

Rami Komrokji, MD: You bring up the most important point, which is as those models evolve, what’s the impact? Realistically, all we have now is transplant. So you’re always trying to make a decision, am I going to transplant those patients? Or what’s the optimal timing of transplant for those patients? I think that’s the question now, if we risk-stratify patients, or upstage the patient risk, are we going to take those patients to transplant? I think your point also is good, that maybe we should think of the patient’s age, and the other factors in that equation, as well. But there is no doubt, I think we saw today at the ASH [American Society of Hematology] annual meeting 2 or 3 presentations showing validation for the IPSS-M. The question is, how do we translate that to practice? I think you asked questions about what happens if you upstage patients, what’s the impact of treatment on those cases?

Guillermo Garcia-Manero, MD: When the IPSS was designed, people were not treated. That cohort, as far as I understand, really, is the natural history of this disease. I was part of the IPSS-R, but what is clear is that, now, on this IPSS-M, the data you beautifully presented, all those patients are treated. And the question is, how do we control for the effect of therapy? Maybe you are an excellent clinician, your patients do very well, etc, so how many were transplanted or not? So, I think at some point, this calls for a bit deeper detail into how these patients were treated.

But I think Dr Platzbecker said something that is critical. That is, we’re stagnated in terms of the therapies we have. I think this is very important analysis, but as we develop, hopefully, more powerful therapies, we will need to learn how to deploy maybe some therapy that starts improving response, and survival. People are talking already, can we look at cytogenetic responses, molecular responses, MRD [minimal residual disease], total therapy, etc when we try to look at it. I think we are starting, and hopefully, some of these clinical trials we’re doing will start giving us that opportunity, and measure again these biomarkers in the context of effective therapy, which we don’t have right at this moment, except for transplant.

Transcript edited for clarity.