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

In an interview with Targeted Oncology, Rami Komrokji, MD, vice chair of the Malignant Hematology Department at Moffitt Cancer Center and professor of medicine and oncologic sciences at the University of South Florida College of Medicine in Tampa, addresses how prognostic scoring systems are used to stratify risk in myelodysplastic syndromes and whether the Revised International Prognostic Scoring System (IPSS-R) and Molecular International Prognostic Scoring System (IPSS-M) consistently align. He begins by noting that myelodysplastic syndrome staging does not follow the TNM framework used in solid tumors, and that the field has evolved through successive iterations of the IIPSS. 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 the scoring system used, patients are ultimately divided into 2 clinically actionable categories: lower risk and higher risk. In the IPSS-M, the first 3 tiers—very low, low, and moderate low—constitute lower-risk disease, and 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 tends to up-stage patients, relative to older systems, meaning some individuals previously classified as lower risk will be reclassified, but the majority will 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.