{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:19:32Z","timestamp":1787019572173,"version":"build-2736575974"},"reference-count":40,"publisher":"American Society of Hematology","issue":"24","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,12,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The standard prognostic marker for multiple myeloma (MM) patients is the revised International Staging System (R-ISS). However, there is room for improvement in guiding treatment. This applies particularly to older patients, in whom the benefit\/risk ratio is reduced because of comorbidities and subsequent side effects. We hypothesized that adding gene-expression data to R-ISS would generate a stronger marker. This was tested by combining R-ISS with the SKY92 classifier (SKY-RISS). The HOVON-87\/NMSG-18 trial (EudraCT: 2007-004007-34) compared melphalan-prednisone-thalidomide followed by thalidomide maintenance (MPT-T) with melphalan-prednisone-lenalidomide followed by lenalidomide maintenance (MPR-R). From this trial, 168 patients with available R-ISS status and gene-expression profiles were analyzed. R-ISS stages I, II, and III were assigned to 8%, 75%, and 7% of patients, respectively (3-year overall survival [OS] rates: 80%, 65%, 33%, P = 8 \u00d7 10\u22123). Using the SKY92 classifier, 13% of patients were high risk (HR) (3-year OS rates: standard risk [SR], 70%; HR, 28%; P &amp;lt; .001). Combining SKY92 with R-ISS resulted in 3 risk groups: SKY-RISS I (SKY-SR + R-ISS-I; 15%), SKY-RISS III (SKY-HR + R-ISS-II\/III; 11%), and SKY-RISS II (all other patients; 74%). The 3-year OS rates for SKY-RISS I, II, and III are 88%, 66%, and 26%, respectively (P = 6 \u00d7 10\u22127). The SKY-RISS model was validated in older patients from the CoMMpass dataset. Moreover, SKY-RISS demonstrated predictive potential: HR patients appeared to benefit from MPR-R over MPT-T (median OS, 55 and 14 months, respectively). Combined, SKY92 and R-ISS classify patients more accurately. Additionally, benefit was observed for MPR-R over MPT-T in SKY92-RISS HR patients only.<\/jats:p>","DOI":"10.1182\/bloodadvances.2020002838","type":"journal-article","created":{"date-parts":[[2020,12,19]],"date-time":"2020-12-19T00:45:26Z","timestamp":1608338726000},"page":"6298-6309","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":33,"title":["Prognostic and predictive performance of R-ISS with SKY92 in older patients with multiple myeloma: the HOVON-87\/NMSG-18 trial"],"prefix":"10.1182","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3703-1762","authenticated-orcid":false,"given":"Rowan","family":"Kuiper","sequence":"first","affiliation":[{"name":"Department of Hematology, Erasmus Medical Center, Cancer Institute, Rotterdam, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Zweegman","sequence":"additional","affiliation":[{"name":"Department of Hematology, Amsterdam University Medical Center, Amsterdam, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"van Duin","sequence":"additional","affiliation":[{"name":"Department of Hematology, Erasmus Medical Center, Cancer Institute, Rotterdam, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6096-5635","authenticated-orcid":false,"given":"Martin H.","family":"van Vliet","sequence":"additional","affiliation":[{"name":"SkylineDx, Rotterdam, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik H.","family":"van Beers","sequence":"additional","affiliation":[{"name":"SkylineDx, Rotterdam, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belinda","family":"Dumee","sequence":"additional","affiliation":[{"name":"SkylineDx, Rotterdam, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Vermeulen","sequence":"additional","affiliation":[{"name":"Department of Hematology, Erasmus Medical Center, Cancer Institute, Rotterdam, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasper","family":"Koenders","sequence":"additional","affiliation":[{"name":"Department of Hematology, Erasmus Medical Center, Cancer Institute, Rotterdam, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bronno","family":"van der Holt","sequence":"additional","affiliation":[{"name":"HOVON Data Center, Department of Hematology, Erasmus Medical Center, Cancer Institute, Rotterdam, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heleen","family":"Visser-Wisselaar","sequence":"additional","affiliation":[{"name":"HOVON Data Center, Department of Hematology, Erasmus Medical Center, Cancer Institute, Rotterdam, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7715-4548","authenticated-orcid":false,"given":"Markus","family":"Hansson","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Sk\u00e5ne University Hospital, Lund, Sweden;"},{"name":"Department of Hematology, Sahlgrenska University Hospital, G\u00f6teborg, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette W. G.","family":"van der Velden","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Martini Hospital, Groningen, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Berna","family":"Beverloo","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9196-7430","authenticated-orcid":false,"given":"Marian","family":"Stevens-Kroef","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark-David","family":"Levin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Albert Schweitzer Hospital, Dordrecht, The Netherlands; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemiek","family":"Broijl","sequence":"additional","affiliation":[{"name":"Department of Hematology, Erasmus Medical Center, Cancer Institute, Rotterdam, The 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