Purpose: Myelodysplastic syndromes (MDS) are heterogeneous myeloid neoplasms in which a risk-adapted treatment strategy is needed. Recently, a new clinical-molecular prognostic model, the Molecular International Prognostic Scoring System (IPSS-M) was proposed to improve the prediction of clinical outcome of the currently available tool (Revised International Prognostic Scoring System [IPSS-R]). We aimed to provide an extensive validation of IPSS-M. Methods: A total of 2,876 patients with primary MDS from the GenoMed4All consortium were retrospectively analyzed. Results: IPSS-M improved prognostic discrimination across all clinical end points with respect to IPSS-R (concordance was 0.81 v 0.74 for overall survival and 0.89 v 0.76 for leukemia-free survival, respectively). This was true even in those patients without detectable gene mutations. Compared with the IPSS-R based stratification, the IPSS-M risk group changed in 46% of patients (23.6% and 22.4% of subjects were upstaged and downstaged, respectively).In patients treated with hematopoietic stem cell transplantation (HSCT), IPSS-M significantly improved the prediction of the risk of disease relapse and the probability of post-transplantation survival versus IPSS-R (concordance was 0.76 v 0.60 for overall survival and 0.89 v 0.70 for probability of relapse, respectively). In high-risk patients treated with hypomethylating agents (HMA), IPSS-M failed to stratify individual probability of response; response duration and probability of survival were inversely related to IPSS-M risk.Finally, we tested the accuracy in predicting IPSS-M when molecular information was missed and we defined a minimum set of 15 relevant genes associated with high performance of the score. Conclusion: 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.
Real-World Validation of Molecular International Prognostic Scoring System for Myelodysplastic Syndromes / Sauta, Elisabetta; Robin, Marie; Bersanelli, Matteo; Travaglino, Erica; Meggendorfer, Manja; Zhao, Lin-Pierre; Caballero Berrocal, Juan Carlos; Sala, Claudia; Maggioni, Giulia; Bernardi, Massimo; Di Grazia, Carmen; Vago, Luca; Rivoli, Giulia; Borin, Lorenza; D'Amico, Saverio; Tentori, Cristina Astrid; Ubezio, Marta; Campagna, Alessia; Russo, Antonio; Mannina, Daniele; Lanino, Luca; Chiusolo, Patrizia; Giaccone, Luisa; Voso, Maria Teresa; Riva, Marta; Oliva, Esther Natalie; Zampini, Matteo; Riva, Elena; Nibourel, Olivier; Bicchieri, Marilena; Bolli, Niccolo'; Rambaldi, Alessandro; Passamonti, Francesco; Savevski, Victor; Santoro, Armando; Germing, Ulrich; Kordasti, Shahram; Santini, Valeria; Diez-Campelo, Maria; Sanz, Guillermo; Sole, Francesc; Kern, Wolfgang; Platzbecker, Uwe; Ades, Lionel; Fenaux, Pierre; Haferlach, Torsten; Castellani, Gastone; Della Porta, Matteo Giovanni. - In: JOURNAL OF CLINICAL ONCOLOGY. - ISSN 0732-183X. - 41:15(2023), pp. 2827-2842. [10.1200/JCO.22.01784]
Real-World Validation of Molecular International Prognostic Scoring System for Myelodysplastic Syndromes
Russo, Antonio;Kordasti, ShahramMembro del Collaboration Group
;
2023-01-01
Abstract
Purpose: Myelodysplastic syndromes (MDS) are heterogeneous myeloid neoplasms in which a risk-adapted treatment strategy is needed. Recently, a new clinical-molecular prognostic model, the Molecular International Prognostic Scoring System (IPSS-M) was proposed to improve the prediction of clinical outcome of the currently available tool (Revised International Prognostic Scoring System [IPSS-R]). We aimed to provide an extensive validation of IPSS-M. Methods: A total of 2,876 patients with primary MDS from the GenoMed4All consortium were retrospectively analyzed. Results: IPSS-M improved prognostic discrimination across all clinical end points with respect to IPSS-R (concordance was 0.81 v 0.74 for overall survival and 0.89 v 0.76 for leukemia-free survival, respectively). This was true even in those patients without detectable gene mutations. Compared with the IPSS-R based stratification, the IPSS-M risk group changed in 46% of patients (23.6% and 22.4% of subjects were upstaged and downstaged, respectively).In patients treated with hematopoietic stem cell transplantation (HSCT), IPSS-M significantly improved the prediction of the risk of disease relapse and the probability of post-transplantation survival versus IPSS-R (concordance was 0.76 v 0.60 for overall survival and 0.89 v 0.70 for probability of relapse, respectively). In high-risk patients treated with hypomethylating agents (HMA), IPSS-M failed to stratify individual probability of response; response duration and probability of survival were inversely related to IPSS-M risk.Finally, we tested the accuracy in predicting IPSS-M when molecular information was missed and we defined a minimum set of 15 relevant genes associated with high performance of the score. Conclusion: 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
