IPSS-R vs IPSS-M: Refining Risk and Treatment in MDS

In an interview with Targeted Oncology, Dr Rami Komrokji, vice chair in the Malignant Hematology Department of Moffitt Cancer Center addresses how prognostic scoring systems are used to stratify risk in myelodysplastic syndromes and whether the IPSS-R and IPSS-M consistently align. He begins by noting that MDS staging does not follow the TNM framework used in solid tumors, and that the field has evolved through successive iterations of the International Prognostic Scoring System. Each version incorporates additional variables—from cytopenias, blast percentage, and cytogenetics in earlier models to molecular data in the most recent IPSS-M—with each iteration refining prognostic groupings and outcomes.

Regardless of which scoring system is applied, patients are ultimately divided into 2 clinically actionable categories: lower risk and higher risk. In the IPSS-M, the first three tiers—very low, low, and moderate low—constitute lower-risk disease, and Dr Komrokji notes that even with the more granular molecular model, approximately 58% of patients still fall into this category. He acknowledges that the IPSS-M does tend to upstage patients relative to older systems, meaning some individuals previously classified as lower risk will be reclassified, but the majority remain in the lower-risk group.

Dr Komrokji emphasizes that the primary curative option in MDS is allogeneic stem cell transplant, now feasible for patients up to age 75, carrying a 40% to 50% cure rate but also a 10% to 20% treatment-related mortality. This risk-benefit calculation means that higher-risk patients are directed toward transplant promptly, while lower-risk patients are managed in a stepwise fashion. The IPSS-M has proven particularly valuable in refining transplant timing, shifting the decision point for roughly one-third of patients.

He cautions, however, that an upstaged IPSS-M score should not automatically translate into higher-risk treatment strategies. For patients who are not transplant candidates—such as an 85-year-old with anemia—escalating to hypomethylating agents is not warranted solely on the basis of a higher molecular score, since those agents improve blood counts rather than induce remissions, and their benefit must be weighed carefully against the patient's overall clinical picture.