Prognostic Performance of a Molecular International Prognostic Scoring System for MDS

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In a European study reported in the Journal of Clinical Oncology, Sauta et al found that the recently devised Molecular International Prognostic Scoring System (IPSS-M) had improved prognostic ability vs the standard Revised International Prognostic Scoring System (IPSS-R) in patients with myelodysplastic syndromes (MDS).

Study Details

The study involved retrospective analysis of data from 2,876 patients with primary MDS from the European GenoMed4All consortium using IPSS-M and IPSS-R. The date range for diagnosis was 1999 to 2018; follow-up was updated in December 2020. The median follow-up was 37.5 months (95% confidence interval [CI] = 36.2–38.8 months).

Key Findings

With the use of IPSS-M, 10% of patients were classified as very low risk, 28% as low risk, 11% as moderate low risk, 11% as moderate high risk, 19% as high risk, and 22% as very high risk. With the use of IPSS-R, 10% of patients were classified as very low risk, 28% as low risk, 21% as intermediate risk, 21% as high risk, and 20% as very high risk.

IPSS-M improved prognostic discrimination vs IPSS-R for outcomes, with a concordance of 0.81 (95% CI = 0.79–0.82) vs 0.74 (95% CI = 0.73–0.76) for overall survival (P < .001 on multivariate analysis) and 0.89 (95% CI = 0.87–0.91) vs 0.76 (95% CI = 0.73–0.79) for leukemia-free survival (P <.001 on multivariate analysis). These relationships were observed even among patients without detectable gene mutations.

To assess changes in 5:5 risk level stratifications, the moderate-low and moderate-high categories were merged to a moderate category in IPSS-M. Overall, compared with IPSS-R stratification, the IPSS-M risk group changed in 46% of patients, with 24% of patients upstaged and 22% downstaged.

Among 964 patients receiving hematopoietic stem cell transplantation (HSCT), IPSS-M significantly improved the prediction of risk of disease relapse (concordance = 0.89 vs 0.70; P < .001 on multivariate analysis) and probability of posttransplantation overall survival (concordance = 0.76 vs 0.60; P < .001 on multivariate analysis).  

Among 268 high-risk patients treated with hypomethylating agents (HMA), IPSS-M did not distinguish the likelihood of overall response according to risk group (overall P = .19). IPSS-M successfully stratified overall survival according to risk group (overall P = .018).

An analysis testing the accuracy of IPSS-M when molecular information was missing defined a minimum set of 15 relevant genes associated with high performance of the scoring system.

The investigators concluded, “IPSS-M improves MDS prognostication and might result in a more effective selection of candidates to HSCT. Additional factors other than gene mutations can be involved in determining HMA sensitivity. The definition of a minimum set of relevant genes may facilitate the clinical implementation of the score.”

Matteo Giovanni Della Porta, MD, of IRCCS Humanitas Clinical & Research Center and Department of Biomedical Sciences, Humanitas University, Milan, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was conducted by the GenoMed4all consortium and supported by EuroBloodNET, AIRC Foundation, Beat Leukemia Foundation, and others. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.