Dr Elli Papaemmanuil Explains Novel Prognostication, Molecular Classification System for MDS

The Molecular International Prognosis Scoring System is a novel risk estimation tool for myelodysplastic syndromes (MDS) that assesses both cytogenetics and gene mutations to enable a molecular base stratification for 100% of patients with MDS, said Elli Papaemmanuil, PhD, assistant professor in computational oncology, Memorial Sloan Kettering Cancer Center.

Papaemmanuil led a Sunday plenary session at the 2022 European Hematology Association (EHA) Congress, titled, “Molecular Classification and Prognostication in MDS.”

Transcript

Can you discuss current prognostic and molecular classification strategies in the management of MDS and findings of your plenary session at EHA2022?

So, typically in myelodysplastic neoplasm, mutations can happen in 2 forms. The one form can be changing chromosomes and what we call chromosomal alterations, and these have been routinely measured clinically through conventional banding analysis or cytogenetics.

More recently, we have come to discover which genes are more frequently mutated in MDS. There are more than 80 genes, and there has been an interest to incorporate gene mutations as biomarkers during the diagnostic workup of patients with MDS.

So, up until now, the backbone of disease classification and stratification has been based on cytogenetic profiling. However, the challenge here is that less than 50% of patients have aberrant cytogenetic profiles. So, for the remaining 50% or 60%, we really do not have any molecular markers to inform both classification and risk stratification.

The work that we will be presenting today incorporates both cytogenetic markers and gene mutations to enable a molecular base stratification for 100% of patients with MDS. So, what we've done is through the International Working Group for Prognosis in MDS. We ascertained over 3000 patients, representative patients with MDS from around the world. We combined clinical and molecular variables.

So, we screened over 100 genes across all patients, and then we looked at correlations between specific gene mutations and outcomes. That allowed us to develop the first molecular risk score for patients with MDS that incorporates findings from cytogenetic abnormalities, as well as information from a minimum set of 32 genes.

So, the IPSS-M score allows us now to improve and refine risk estimation for all patients by using information of both the conventional clinical variables, the cytogenetics, but adding on top of that the gene mutations that are most relevant in separating patients according to their risk status.