Predictors of early morbidity and mortality in newly diagnosed multiple myeloma: data from five randomized, controlled, phase III trials in 3700 patients.

Autor: Mai EK; Department of Internal Medicine V, University Hospital Heidelberg, Heidelberg, Germany. elias.mai@med.uni-heidelberg.de., Hielscher T; Division of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany., Bertsch U; Department of Internal Medicine V, University Hospital Heidelberg, Heidelberg, Germany.; National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, Germany., Salwender HJ; Tumorzentrum Asklepios Hamburg, AK Altona and AK St. Georg, Hamburg, Germany., Zweegman S; Department of Hematology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands., Raab MS; Department of Internal Medicine V, University Hospital Heidelberg, Heidelberg, Germany., Munder M; Department of Internal Medicine III, University Medical Center Mainz, Mainz, Germany., Pantani L; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli', Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Azienda Ospedaliero-Universitaria di Bologna, Università di Bologna, Bologna, Italy., Mancuso K; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli', Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Azienda Ospedaliero-Universitaria di Bologna, Università di Bologna, Bologna, Italy., Brossart P; Department of Internal Medicine III, University Hospital Bonn, Bonn, Germany., Beksac M; Department of Hematology, Ankara University School of Medicine, Ankara, Turkey., Blau IW; Medical Clinic, Charité University Medicine Berlin, Berlin, Germany., Dürig J; Department of Hematology, University Clinic Essen, Essen, Germany., Besemer B; Department of Hematology, Oncology and Immunology, University Hospital Tübingen, Tübingen, Germany., Fenk R; Department of Hematology, Oncology and Clinical Immunology, University Hospital Düsseldorf, Düsseldorf, Germany., Reimer P; Klinik für Hämatologie, Evangelische Kliniken Essen Mitte, Evangelisches Krankenhaus Essen-Werden, Essen, Germany., van der Holt B; HOVON Data Center, Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, Netherlands., Hänel M; Department of Internal Medicine III, Klinikum Chemnitz, Chemnitz, Germany., von Metzler I; Medical Clinic II, University Hospital Frankfurt am Main, Frankfurt am Main, Germany., Graeven U; Department of Internal Medicine I, Hospital Maria Hilf GmbH, Mönchengladbach, Germany., Müller-Tidow C; Department of Internal Medicine V, University Hospital Heidelberg, Heidelberg, Germany., Boccadoro M; Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Turin, Italy., Scheid C; Department of Internal Medicine I, University Hospital Cologne, Cologne, Germany., Dimopoulos MA; Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece., Hillengass J; Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA., Weisel KC; Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Cavo M; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli', Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Azienda Ospedaliero-Universitaria di Bologna, Università di Bologna, Bologna, Italy., Sonneveld P; Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, Netherlands., Goldschmidt H; Department of Internal Medicine V, University Hospital Heidelberg, Heidelberg, Germany.; National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, Germany.
Jazyk: angličtina
Zdroj: Leukemia [Leukemia] 2024 Mar; Vol. 38 (3), pp. 640-647. Date of Electronic Publication: 2023 Dec 07.
DOI: 10.1038/s41375-023-02105-6
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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