Development and Validation of a Cytogenetic Prognostic Index Predicting Survival in Multiple Myeloma

Autor: Philippe Moreau, Philippe Rodon, Marie-Lorraine Chretien, Hervé Avet-Loiseau, Olivier Decaux, Cyrille Hulin, Sabine Brechignac, Hélène Demarquette, Xavier Leleu, Michel Attal, Bruno Royer, Laurent Voillat, Philippe Collet, Jill Corre, Aurore Perrot, Margaret Macro, Frédérique Orsini-Piocelle, François Lifermann, Karim Belhadj, Thierry Facon, Arnaud Jaccard, Valérie Lauwers-Cances, Stephane Minvielle, Mohamad Mohty, Elodie Tournay, Valentine Richez, Mamoun Dib, Jean Fontan, Claudine Sohn
Přispěvatelé: Centre hospitalier universitaire de Nantes (CHU Nantes), Minvielle, Stéphane
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
Oncology
Cancer Research
medicine.medical_specialty
Validation study
Disease free survival
Multivariate analysis
Chromosomes
Human
Pair 21
Trisomy
[SDV.CAN]Life Sciences [q-bio]/Cancer
Risk Assessment
Disease-Free Survival
Translocation
Genetic
03 medical and health sciences
0302 clinical medicine
[SDV.CAN] Life Sciences [q-bio]/Cancer
Internal medicine
medicine
Humans
Survival analysis
Multiple myeloma
ComputingMilieux_MISCELLANEOUS
Aged
030304 developmental biology
0303 health sciences
Extramural
business.industry
ORIGINAL REPORTS
Middle Aged
Gene deletion
Prognosis
medicine.disease
Survival Analysis
3. Good health
Multicenter study
030220 oncology & carcinogenesis
Cytogenetic Analysis
Multivariate Analysis
Chromosomes
Human
Pair 5
Female
Chromosomes
Human
Pair 3
Multiple Myeloma
business
Gene Deletion
Zdroj: Journal of Clinical Oncology
Journal of Clinical Oncology, American Society of Clinical Oncology, 2019, 37 (19), pp.1657-1665. ⟨10.1200/JCO.18.00776⟩
ISSN: 0732-183X
1527-7755
DOI: 10.1200/JCO.18.00776⟩
Popis: PURPOSE The wide heterogeneity in multiple myeloma (MM) outcome is driven mainly by cytogenetic abnormalities. The current definition of high-risk profile is restrictive and oversimplified. To adapt MM treatment to risk, we need to better define a cytogenetic risk classification. To address this issue, we simultaneously examined the prognostic impact of del(17p); t(4;14); del(1p32); 1q21 gain; and trisomies 3, 5, and 21 in a cohort of newly diagnosed patients with MM. METHODS Data were obtained from 1,635 patients enrolled in four trials implemented by the Intergroupe Francophone du Myélome. The oldest collection of data were used for model development and internal validation. For external validation, one of the two independent data sets was used to assess the performance of the model in patients treated with more current regimens. Six cytogenetic abnormalities were identified as clinically relevant, and a prognostic index (PI) that was based on the parameter estimates of the multivariable Cox model was computed for all patients. RESULTS In all data sets, a higher PI was consistently associated with a poor survival outcome. Dependent on the validation cohorts used, hazard ratios for patients in the high-risk category for death were between six and 15 times higher than those of patients in the low-risk category. Among patients with t(4;14) or del(17p), we observed a worse survival in those classified in the high-risk category than in those in the intermediate-risk category. The PI showed good performance for discriminating between patients who died and those who survived (Harrell’s concordance index greater than 70%). CONCLUSION The cytogenetic PI improves the classification of newly diagnosed patients with MM in the high-risk group compared with current classifications. These findings may facilitate the development of risk-adapted treatment strategies.
Databáze: OpenAIRE
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