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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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Main Authors: Mai, Elias K. (Author) , Hielscher, Thomas (Author) , Bertsch, Uta (Author) , Salwender, Hans (Author) , Zweegman, Sonja (Author) , Raab, Marc-Steffen (Author) , Munder, Markus (Author) , Pantani, Lucia (Author) , Mancuso, Katia (Author) , Brossart, Peter (Author) , Beksaç, Meral (Author) , Blau, Igor-Wolfgang (Author) , Dürig, Jan (Author) , Besemer, Britta (Author) , Fenk, Roland (Author) , Reimer, Peter (Author) , van der Holt, Bronno (Author) , Hänel, Mathias (Author) , von Metzler, Ivana (Author) , Graeven, Ullrich (Author) , Müller-Tidow, Carsten (Author) , Boccadoro, Mario (Author) , Scheid, Christoph (Author) , Dimopoulos, Meletios A. (Author) , Hillengaß, Jens (Author) , Weisel, Katja (Author) , Cavo, Michele (Author) , Sonneveld, Pieter (Author) , Goldschmidt, Hartmut (Author)
Format: Article (Journal)
Language:English
Published: 07 December 2023
In: Leukemia
Year: 2023, Pages: 1-8
ISSN:1476-5551
DOI:10.1038/s41375-023-02105-6
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41375-023-02105-6
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41375-023-02105-6
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Author Notes:Elias K. Mai, Thomas Hielscher, Uta Bertsch, Hans J. Salwender, Sonja Zweegman, Marc S. Raab, Markus Munder, Lucia Pantani, Katia Mancuso, Peter Brossart, Meral Beksac, Igor W. Blau, Jan Dürig, Britta Besemer, Roland Fenk, Peter Reimer, Bronno van der Holt, Mathias Hänel, Ivana von Metzler, Ullrich Graeven, Carsten Müller-Tidow, Mario Boccadoro, Christof Scheid, Meletios A. Dimopoulos, Jens Hillengass, Katja C. Weisel, Michele Cavo, Pieter Sonneveld and Hartmut Goldschmidt
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Summary: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.
Item Description:Gesehen am 09.02.2024
Physical Description:Online Resource
ISSN:1476-5551
DOI:10.1038/s41375-023-02105-6

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