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In this retrospective, multicohort study, we collected clinical and genetic data from 1792 NDMM patients and identified the prognostic impact of all features. Using the top\u2010ranked predictive features, a weighted Myeloma Prognostic Score System (MPSS) risk model was formulated and validated to predict overall survival (OS). In the training cohort, elevated lactate dehydrogenase level (LDH), International Staging System (ISS) Stage III, thrombocytopenia, and cumulative high\u2010risk cytogenetic aberration (HRA) numbers were found to have independent prognostic significance. Each risk factor was defined as its weighted value respectively according to their hazard ratio for OS (thrombocytopenia 2, elevated LDH 1, ISS III 2, one HRA 1, and \u22652 HRA 2, points). Patients were further stratified into four risk groups: MPSS I (22.5%, 0 points), II (17.6%, 1 points), III (38.6%, 2\u20133 points), and IV (21.3%, 4\u20137 points). MPSS risk stratification showed optimal discrimination, as well as calibration, of four risk groups with median OS of 91.0, 69.8, 45.0, and 28.0\u2009months, for patients in MPSS I to IV groups (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001), respectively. Importantly, the MPSS model retained its prognostic value in the internal validation cohort and an independent external validation cohort, and exhibited significant risk distribution compared with conventional prognostic models (R\u2010ISS, R2\u2010ISS, and MASS). Utilization of the MPSS model in clinical practice could improve risk estimation in NDMM patients, thus prompting individualized treatment strategies.<\/jats:p>","DOI":"10.1002\/ajh.27207","type":"journal-article","created":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T07:55:11Z","timestamp":1705910111000},"page":"523-533","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Development and validation of an individualized and weighted Myeloma Prognostic Score System (<scp>MPSS<\/scp>) in patients with newly diagnosed multiple myeloma"],"prefix":"10.1002","volume":"99","author":[{"given":"Xuehan","family":"Mao","sequence":"first","affiliation":[{"name":"National Clinical Research Center for Blood Diseases, State Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Institute of Hematology &amp; Blood Diseases Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Tianjin China"},{"name":"Tianjin Institutes of Health Science  Tianjin China"},{"name":"Department of Hematology Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University  Beijing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6813-7810","authenticated-orcid":false,"given":"Wenqiang","family":"Yan","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Blood Diseases, State Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Institute of Hematology &amp; Blood Diseases Hospital Chinese Academy of Medical Sciences &amp; Peking Union Medical College  Tianjin China"},{"name":"Tianjin Institutes of Health Science  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8327-9777","authenticated-orcid":false,"given":"David","family":"Mery","sequence":"additional","affiliation":[{"name":"Myeloma Center, Winthrop P. 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