Predictors of early morbidity and mortality in newly diagnosed multiple myeloma: data from five randomized, controlled, phase III trials in 3700 patients
Early morbidity and mortality affect patient outcomes in multiple myeloma. Thus, we dissected the incidence and causes of morbidity/mortality during induction therapy (IT) for newly diagnosed multiple myeloma (NDMM), and developed/validated a predictive risk score. We evaluated 3700 transplant-eligi...
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| Veröffentlicht in: | Leukemia 2024-03, Vol.38 (3), p.640-647 |
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| creator | Mai, Elias K. Hielscher, Thomas Bertsch, Uta Salwender, Hans J. Zweegman, Sonja Raab, Marc S. Munder, Markus Pantani, Lucia Mancuso, Katia Brossart, Peter Beksac, Meral Blau, Igor W. Dürig, Jan Besemer, Britta Fenk, Roland Reimer, Peter van der Holt, Bronno Hänel, Mathias von Metzler, Ivana Graeven, Ullrich Müller-Tidow, Carsten Boccadoro, Mario Scheid, Christof Dimopoulos, Meletios A. Hillengass, Jens Weisel, Katja C. Cavo, Michele Sonneveld, Pieter Goldschmidt, Hartmut |
| description | Early morbidity and mortality affect patient outcomes in multiple myeloma. Thus, we dissected the incidence and causes of morbidity/mortality during induction therapy (IT) for newly diagnosed multiple myeloma (NDMM), and developed/validated a predictive risk score. We evaluated 3700 transplant-eligible NDMM patients treated in 2005–2020 with novel agent-based triplet/quadruplet IT. Primary endpoints were severe infections, death, or a combination of both. Patients were divided in a training (
n
= 1333) and three validation cohorts (
n
= 2367). During IT, 11.8%, 1.8%, and 12.5% of patients in the training cohort experienced severe infections, death, or both, respectively. Four major, baseline risk factors for severe infection/death were identified: low platelet count (1), and age (>60 years). A risk score (1 risk factor=1 point) stratified patients in low (39.5%; 0 points), intermediate (41.9%; 1 point), and high (18.6%; ≥2 points) risk. The risk for severe infection/death increased from 7.7% vs. 11.5% vs. 23.3% in the low- vs. intermediate- vs. high-risk groups (
p
|
| doi_str_mv | 10.1038/s41375-023-02105-6 |
| format | Article |
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n
= 1333) and three validation cohorts (
n
= 2367). During IT, 11.8%, 1.8%, and 12.5% of patients in the training cohort experienced severe infections, death, or both, respectively. Four major, baseline risk factors for severe infection/death were identified: low platelet count (<150/nL), ISS III, higher WHO performance status (>1), and age (>60 years). A risk score (1 risk factor=1 point) stratified patients in low (39.5%; 0 points), intermediate (41.9%; 1 point), and high (18.6%; ≥2 points) risk. The risk for severe infection/death increased from 7.7% vs. 11.5% vs. 23.3% in the low- vs. intermediate- vs. high-risk groups (
p
< 0.001). The risk score was independently validated in three trials incorporating quadruplet IT with an anti-CD38 antibody. Our analyses established a robust and easy-to-use score to identify NDMM patients at risk of severe infection/death, covering the latest quadruplet induction therapies. Trial registrations: HOVON-65/GMMG-HD4: EudraCT No. 2004-000944-26. GMMG-MM5: EudraCT No. 2010-019173-16. GMMG-HD6: NCT02495922. EMN02/HOVON-95: NCT01208766. GMMG-HD7: NCT03617731.</description><identifier>ISSN: 0887-6924</identifier><identifier>ISSN: 1476-5551</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/s41375-023-02105-6</identifier><identifier>PMID: 38062124</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>692/499 ; 692/699/67/1990/804 ; Antibodies ; Cancer Research ; CD38 antigen ; Clinical trials ; Critical Care Medicine ; Death ; Hematology ; Induction therapy ; Infections ; Intensive ; Internal Medicine ; Medicine ; Medicine & Public Health ; Morbidity ; Mortality ; Multiple myeloma ; Oncology ; Risk factors ; Risk groups ; Training</subject><ispartof>Leukemia, 2024-03, Vol.38 (3), p.640-647</ispartof><rights>The Author(s) 2023</rights><rights>2023. The Author(s).</rights><rights>The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c475t-eaecf5397c97da916cfa2ebda4391b3761f9b1c20266bf2806250e312b0d9fad3</citedby><cites>FETCH-LOGICAL-c475t-eaecf5397c97da916cfa2ebda4391b3761f9b1c20266bf2806250e312b0d9fad3</cites><orcidid>0000-0002-1169-0129 ; 0000-0002-7166-5232 ; 0000-0003-4181-6922 ; 0000-0003-0961-0035 ; 0000-0001-6082-7710 ; 0000-0001-9422-6614 ; 0000-0001-6414-2671 ; 0000-0003-1797-8657 ; 0000-0001-8130-5209 ; 0000-0002-0808-2237 ; 0000-0001-8990-3254 ; 0000-0001-7803-0814 ; 0000-0003-4514-3227 ; 0000-0002-6226-1252</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41375-023-02105-6$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41375-023-02105-6$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,777,781,882,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38062124$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mai, Elias K.</creatorcontrib><creatorcontrib>Hielscher, Thomas</creatorcontrib><creatorcontrib>Bertsch, Uta</creatorcontrib><creatorcontrib>Salwender, Hans J.</creatorcontrib><creatorcontrib>Zweegman, Sonja</creatorcontrib><creatorcontrib>Raab, Marc S.</creatorcontrib><creatorcontrib>Munder, Markus</creatorcontrib><creatorcontrib>Pantani, Lucia</creatorcontrib><creatorcontrib>Mancuso, Katia</creatorcontrib><creatorcontrib>Brossart, Peter</creatorcontrib><creatorcontrib>Beksac, Meral</creatorcontrib><creatorcontrib>Blau, Igor W.</creatorcontrib><creatorcontrib>Dürig, Jan</creatorcontrib><creatorcontrib>Besemer, Britta</creatorcontrib><creatorcontrib>Fenk, Roland</creatorcontrib><creatorcontrib>Reimer, Peter</creatorcontrib><creatorcontrib>van der Holt, Bronno</creatorcontrib><creatorcontrib>Hänel, Mathias</creatorcontrib><creatorcontrib>von Metzler, Ivana</creatorcontrib><creatorcontrib>Graeven, Ullrich</creatorcontrib><creatorcontrib>Müller-Tidow, Carsten</creatorcontrib><creatorcontrib>Boccadoro, Mario</creatorcontrib><creatorcontrib>Scheid, Christof</creatorcontrib><creatorcontrib>Dimopoulos, Meletios A.</creatorcontrib><creatorcontrib>Hillengass, Jens</creatorcontrib><creatorcontrib>Weisel, Katja C.</creatorcontrib><creatorcontrib>Cavo, Michele</creatorcontrib><creatorcontrib>Sonneveld, Pieter</creatorcontrib><creatorcontrib>Goldschmidt, Hartmut</creatorcontrib><title>Predictors of early morbidity and mortality in newly diagnosed multiple myeloma: data from five randomized, controlled, phase III trials in 3700 patients</title><title>Leukemia</title><addtitle>Leukemia</addtitle><addtitle>Leukemia</addtitle><description>Early morbidity and mortality affect patient outcomes in multiple myeloma. Thus, we dissected the incidence and causes of morbidity/mortality during induction therapy (IT) for newly diagnosed multiple myeloma (NDMM), and developed/validated a predictive risk score. We evaluated 3700 transplant-eligible NDMM patients treated in 2005–2020 with novel agent-based triplet/quadruplet IT. Primary endpoints were severe infections, death, or a combination of both. Patients were divided in a training (
n
= 1333) and three validation cohorts (
n
= 2367). During IT, 11.8%, 1.8%, and 12.5% of patients in the training cohort experienced severe infections, death, or both, respectively. Four major, baseline risk factors for severe infection/death were identified: low platelet count (<150/nL), ISS III, higher WHO performance status (>1), and age (>60 years). A risk score (1 risk factor=1 point) stratified patients in low (39.5%; 0 points), intermediate (41.9%; 1 point), and high (18.6%; ≥2 points) risk. The risk for severe infection/death increased from 7.7% vs. 11.5% vs. 23.3% in the low- vs. intermediate- vs. high-risk groups (
p
< 0.001). The risk score was independently validated in three trials incorporating quadruplet IT with an anti-CD38 antibody. Our analyses established a robust and easy-to-use score to identify NDMM patients at risk of severe infection/death, covering the latest quadruplet induction therapies. Trial registrations: HOVON-65/GMMG-HD4: EudraCT No. 2004-000944-26. GMMG-MM5: EudraCT No. 2010-019173-16. GMMG-HD6: NCT02495922. EMN02/HOVON-95: NCT01208766. 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Britta</au><au>Fenk, Roland</au><au>Reimer, Peter</au><au>van der Holt, Bronno</au><au>Hänel, Mathias</au><au>von Metzler, Ivana</au><au>Graeven, Ullrich</au><au>Müller-Tidow, Carsten</au><au>Boccadoro, Mario</au><au>Scheid, Christof</au><au>Dimopoulos, Meletios A.</au><au>Hillengass, Jens</au><au>Weisel, Katja C.</au><au>Cavo, Michele</au><au>Sonneveld, Pieter</au><au>Goldschmidt, Hartmut</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Predictors of early morbidity and mortality in newly diagnosed multiple myeloma: data from five randomized, controlled, phase III trials in 3700 patients</atitle><jtitle>Leukemia</jtitle><stitle>Leukemia</stitle><addtitle>Leukemia</addtitle><date>2024-03-01</date><risdate>2024</risdate><volume>38</volume><issue>3</issue><spage>640</spage><epage>647</epage><pages>640-647</pages><issn>0887-6924</issn><issn>1476-5551</issn><eissn>1476-5551</eissn><abstract>Early morbidity and mortality affect patient outcomes in multiple myeloma. Thus, we dissected the incidence and causes of morbidity/mortality during induction therapy (IT) for newly diagnosed multiple myeloma (NDMM), and developed/validated a predictive risk score. We evaluated 3700 transplant-eligible NDMM patients treated in 2005–2020 with novel agent-based triplet/quadruplet IT. Primary endpoints were severe infections, death, or a combination of both. Patients were divided in a training (
n
= 1333) and three validation cohorts (
n
= 2367). During IT, 11.8%, 1.8%, and 12.5% of patients in the training cohort experienced severe infections, death, or both, respectively. Four major, baseline risk factors for severe infection/death were identified: low platelet count (<150/nL), ISS III, higher WHO performance status (>1), and age (>60 years). A risk score (1 risk factor=1 point) stratified patients in low (39.5%; 0 points), intermediate (41.9%; 1 point), and high (18.6%; ≥2 points) risk. The risk for severe infection/death increased from 7.7% vs. 11.5% vs. 23.3% in the low- vs. intermediate- vs. high-risk groups (
p
< 0.001). The risk score was independently validated in three trials incorporating quadruplet IT with an anti-CD38 antibody. Our analyses established a robust and easy-to-use score to identify NDMM patients at risk of severe infection/death, covering the latest quadruplet induction therapies. Trial registrations: HOVON-65/GMMG-HD4: EudraCT No. 2004-000944-26. GMMG-MM5: EudraCT No. 2010-019173-16. GMMG-HD6: NCT02495922. EMN02/HOVON-95: NCT01208766. GMMG-HD7: NCT03617731.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>38062124</pmid><doi>10.1038/s41375-023-02105-6</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-1169-0129</orcidid><orcidid>https://orcid.org/0000-0002-7166-5232</orcidid><orcidid>https://orcid.org/0000-0003-4181-6922</orcidid><orcidid>https://orcid.org/0000-0003-0961-0035</orcidid><orcidid>https://orcid.org/0000-0001-6082-7710</orcidid><orcidid>https://orcid.org/0000-0001-9422-6614</orcidid><orcidid>https://orcid.org/0000-0001-6414-2671</orcidid><orcidid>https://orcid.org/0000-0003-1797-8657</orcidid><orcidid>https://orcid.org/0000-0001-8130-5209</orcidid><orcidid>https://orcid.org/0000-0002-0808-2237</orcidid><orcidid>https://orcid.org/0000-0001-8990-3254</orcidid><orcidid>https://orcid.org/0000-0001-7803-0814</orcidid><orcidid>https://orcid.org/0000-0003-4514-3227</orcidid><orcidid>https://orcid.org/0000-0002-6226-1252</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0887-6924 |
| ispartof | Leukemia, 2024-03, Vol.38 (3), p.640-647 |
| issn | 0887-6924 1476-5551 1476-5551 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10912032 |
| source | Springer Nature - Complete Springer Journals |
| subjects | 692/499 692/699/67/1990/804 Antibodies Cancer Research CD38 antigen Clinical trials Critical Care Medicine Death Hematology Induction therapy Infections Intensive Internal Medicine Medicine Medicine & Public Health Morbidity Mortality Multiple myeloma Oncology Risk factors Risk groups Training |
| title | Predictors of early morbidity and mortality in newly diagnosed multiple myeloma: data from five randomized, controlled, phase III trials in 3700 patients |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-21T04%3A01%3A15IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Predictors%20of%20early%20morbidity%20and%20mortality%20in%20newly%20diagnosed%20multiple%20myeloma:%20data%20from%20five%20randomized,%20controlled,%20phase%20III%20trials%20in%203700%20patients&rft.jtitle=Leukemia&rft.au=Mai,%20Elias%20K.&rft.date=2024-03-01&rft.volume=38&rft.issue=3&rft.spage=640&rft.epage=647&rft.pages=640-647&rft.issn=0887-6924&rft.eissn=1476-5551&rft_id=info:doi/10.1038/s41375-023-02105-6&rft_dat=%3Cproquest_pubme%3E2937158135%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2937158135&rft_id=info:pmid/38062124&rfr_iscdi=true |