Prognostic and predictive performance of R-ISS with SKY92 in older patients with multiple myeloma: the HOVON-87/NMSG-18 trial
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 subs...
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| creator | Kuiper, Rowan Zweegman, Sonja van Duin, Mark van Vliet, Martin H. van Beers, Erik H. Dumee, Belinda Vermeulen, Michael Koenders, Jasper van der Holt, Bronno Visser-Wisselaar, Heleen Hansson, Markus van der Velden, Annette W.G. Beverloo, H. Berna Stevens-Kroef, Marian Levin, Mark-David Broijl, Annemiek Waage, Anders Sonneveld, Pieter |
| description | 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 × 10−3). Using the SKY92 classifier, 13% of patients were high risk (HR) (3-year OS rates: standard risk [SR], 70%; HR, 28%; P < .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 × 10−7). 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.
•Combining SKY92 with R-ISS results in a superior prognostic marker compared with either marker separately.•SKY-RISS acts as an immunomodulatory agent predictor. A benefit of MPR-R over MPT-T was seen for HR patients only.
[Display omitted] |
| doi_str_mv | 10.1182/bloodadvances.2020002838 |
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•Combining SKY92 with R-ISS results in a superior prognostic marker compared with either marker separately.•SKY-RISS acts as an immunomodulatory agent predictor. A benefit of MPR-R over MPT-T was seen for HR patients only.
[Display omitted]</description><identifier>ISSN: 2473-9529</identifier><identifier>EISSN: 2473-9537</identifier><identifier>DOI: 10.1182/bloodadvances.2020002838</identifier><identifier>PMID: 33351127</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Aged ; Humans ; Lenalidomide ; Lymphoid Neoplasia ; Multiple Myeloma - diagnosis ; Multiple Myeloma - drug therapy ; Prognosis ; Thalidomide</subject><ispartof>Blood advances, 2020-12, Vol.4 (24), p.6298-6309</ispartof><rights>2020 The American Society of Hematology</rights><rights>2020 by The American Society of Hematology.</rights><rights>2020 by The American Society of Hematology 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c479t-3f8bae98769757b54d4ccee4333e8a802899ffba08603300941a814f9f2632003</citedby><cites>FETCH-LOGICAL-c479t-3f8bae98769757b54d4ccee4333e8a802899ffba08603300941a814f9f2632003</cites><orcidid>0000-0002-3703-1762 ; 0000-0001-9072-1220 ; 0000-0002-7715-4548 ; 0000-0002-6096-5635 ; 0000-0002-9196-7430</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756986/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756986/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33351127$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kuiper, Rowan</creatorcontrib><creatorcontrib>Zweegman, Sonja</creatorcontrib><creatorcontrib>van Duin, Mark</creatorcontrib><creatorcontrib>van Vliet, Martin H.</creatorcontrib><creatorcontrib>van Beers, Erik H.</creatorcontrib><creatorcontrib>Dumee, Belinda</creatorcontrib><creatorcontrib>Vermeulen, Michael</creatorcontrib><creatorcontrib>Koenders, Jasper</creatorcontrib><creatorcontrib>van der Holt, Bronno</creatorcontrib><creatorcontrib>Visser-Wisselaar, Heleen</creatorcontrib><creatorcontrib>Hansson, Markus</creatorcontrib><creatorcontrib>van der Velden, Annette W.G.</creatorcontrib><creatorcontrib>Beverloo, H. Berna</creatorcontrib><creatorcontrib>Stevens-Kroef, Marian</creatorcontrib><creatorcontrib>Levin, Mark-David</creatorcontrib><creatorcontrib>Broijl, Annemiek</creatorcontrib><creatorcontrib>Waage, Anders</creatorcontrib><creatorcontrib>Sonneveld, Pieter</creatorcontrib><title>Prognostic and predictive performance of R-ISS with SKY92 in older patients with multiple myeloma: the HOVON-87/NMSG-18 trial</title><title>Blood advances</title><addtitle>Blood Adv</addtitle><description>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 × 10−3). Using the SKY92 classifier, 13% of patients were high risk (HR) (3-year OS rates: standard risk [SR], 70%; HR, 28%; P < .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 × 10−7). 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.
•Combining SKY92 with R-ISS results in a superior prognostic marker compared with either marker separately.•SKY-RISS acts as an immunomodulatory agent predictor. A benefit of MPR-R over MPT-T was seen for HR patients only.
[Display omitted]</description><subject>Aged</subject><subject>Humans</subject><subject>Lenalidomide</subject><subject>Lymphoid Neoplasia</subject><subject>Multiple Myeloma - diagnosis</subject><subject>Multiple Myeloma - drug therapy</subject><subject>Prognosis</subject><subject>Thalidomide</subject><issn>2473-9529</issn><issn>2473-9537</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUU1v1DAQtRCIVqV_AfnIJa0_ktjmgAQVtFVLF7GAxMlynEnXyImD7V3UA_8dV9su7amnGWnevDfzHkKYkiNKJTvufAi96TdmspCOGGGEECa5fIb2WS14pRounu96pvbQYUq_CoiKljeKvUR7nPOGUib20d8vMVxPIWVnsZl6PEfonc1uA3iGOIQ43srgMOCv1flyif-4vMLLi5-KYTfh4HuIeDbZwZTTdjiufXazBzzegA-jeYvzCvDZ4sfiqpLi-Orz8rSiEufojH-FXgzGJzi8qwfo-6eP307OqsvF6fnJ-8vK1kLlig-yM6CkaJVoRNfUfW0tQF3eAGlk-V6pYegMkS3hnBBVUyNpPaiBtbzYww_Quy3vvO5G6G25Nhqv5-hGE290ME4_nkxupa_DRgvRtEq2heDNHUEMv9eQsh5dsuC9mSCsky5mM0oUlbxA5RZqY0gpwrCToUTfBqgfBaj_B1hWXz88c7d4H1cBfNgCoJi1cRB1ssV6WzKLYLPug3ta5R-nqrFp</recordid><startdate>20201222</startdate><enddate>20201222</enddate><creator>Kuiper, Rowan</creator><creator>Zweegman, Sonja</creator><creator>van Duin, Mark</creator><creator>van Vliet, Martin H.</creator><creator>van Beers, Erik H.</creator><creator>Dumee, Belinda</creator><creator>Vermeulen, Michael</creator><creator>Koenders, Jasper</creator><creator>van der Holt, Bronno</creator><creator>Visser-Wisselaar, Heleen</creator><creator>Hansson, Markus</creator><creator>van der Velden, Annette W.G.</creator><creator>Beverloo, H. Berna</creator><creator>Stevens-Kroef, Marian</creator><creator>Levin, Mark-David</creator><creator>Broijl, Annemiek</creator><creator>Waage, Anders</creator><creator>Sonneveld, Pieter</creator><general>Elsevier Inc</general><general>American Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3703-1762</orcidid><orcidid>https://orcid.org/0000-0001-9072-1220</orcidid><orcidid>https://orcid.org/0000-0002-7715-4548</orcidid><orcidid>https://orcid.org/0000-0002-6096-5635</orcidid><orcidid>https://orcid.org/0000-0002-9196-7430</orcidid></search><sort><creationdate>20201222</creationdate><title>Prognostic and predictive performance of R-ISS with SKY92 in older patients with multiple myeloma: the HOVON-87/NMSG-18 trial</title><author>Kuiper, Rowan ; Zweegman, Sonja ; van Duin, Mark ; van Vliet, Martin H. ; van Beers, Erik H. ; Dumee, Belinda ; Vermeulen, Michael ; Koenders, Jasper ; van der Holt, Bronno ; Visser-Wisselaar, Heleen ; Hansson, Markus ; van der Velden, Annette W.G. ; Beverloo, H. 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Berna</creatorcontrib><creatorcontrib>Stevens-Kroef, Marian</creatorcontrib><creatorcontrib>Levin, Mark-David</creatorcontrib><creatorcontrib>Broijl, Annemiek</creatorcontrib><creatorcontrib>Waage, Anders</creatorcontrib><creatorcontrib>Sonneveld, Pieter</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Blood advances</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kuiper, Rowan</au><au>Zweegman, Sonja</au><au>van Duin, Mark</au><au>van Vliet, Martin H.</au><au>van Beers, Erik H.</au><au>Dumee, Belinda</au><au>Vermeulen, Michael</au><au>Koenders, Jasper</au><au>van der Holt, Bronno</au><au>Visser-Wisselaar, Heleen</au><au>Hansson, Markus</au><au>van der Velden, Annette W.G.</au><au>Beverloo, H. Berna</au><au>Stevens-Kroef, Marian</au><au>Levin, Mark-David</au><au>Broijl, Annemiek</au><au>Waage, Anders</au><au>Sonneveld, Pieter</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prognostic and predictive performance of R-ISS with SKY92 in older patients with multiple myeloma: the HOVON-87/NMSG-18 trial</atitle><jtitle>Blood advances</jtitle><addtitle>Blood Adv</addtitle><date>2020-12-22</date><risdate>2020</risdate><volume>4</volume><issue>24</issue><spage>6298</spage><epage>6309</epage><pages>6298-6309</pages><issn>2473-9529</issn><eissn>2473-9537</eissn><abstract>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 × 10−3). Using the SKY92 classifier, 13% of patients were high risk (HR) (3-year OS rates: standard risk [SR], 70%; HR, 28%; P < .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 × 10−7). 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.
•Combining SKY92 with R-ISS results in a superior prognostic marker compared with either marker separately.•SKY-RISS acts as an immunomodulatory agent predictor. A benefit of MPR-R over MPT-T was seen for HR patients only.
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| subjects | Aged Humans Lenalidomide Lymphoid Neoplasia Multiple Myeloma - diagnosis Multiple Myeloma - drug therapy Prognosis Thalidomide |
| title | Prognostic and predictive performance of R-ISS with SKY92 in older patients with multiple myeloma: the HOVON-87/NMSG-18 trial |
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