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 ascopubs.org.
