Predictors of early morbidity and mortality in newly diagnosed multiple myeloma: data from five randomized, controlled, phase III trials in 3700 patients
Author:
Mai Elias K.ORCID, Hielscher Thomas, Bertsch Uta, Salwender Hans J.ORCID, Zweegman Sonja, Raab Marc S.ORCID, Munder Markus, Pantani Lucia, Mancuso KatiaORCID, Brossart Peter, Beksac MeralORCID, Blau Igor W., Dürig Jan, Besemer Britta, Fenk Roland, Reimer Peter, van der Holt BronnoORCID, Hänel Mathias, von Metzler Ivana, Graeven UllrichORCID, Müller-Tidow CarstenORCID, Boccadoro MarioORCID, Scheid Christof, Dimopoulos Meletios A.ORCID, Hillengass Jens, Weisel Katja C.ORCID, Cavo MicheleORCID, Sonneveld PieterORCID, Goldschmidt HartmutORCID
Abstract
AbstractEarly 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.
Publisher
Springer Science and Business Media LLC
Subject
Oncology,Cancer Research,Hematology
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