Purpose: Patients with newly diagnosed multiple myeloma (NDMM) show heterogeneous outcomes, and approximately 60% of them are at intermediate-risk according to the Revised International Staging system (R-ISS), the standard-of-care risk stratification model. Moreover, chromosome 1q gain/amplification (1q+) recently proved to be a poor prognostic factor. In this study, we revised the R-ISS by analyzing the additive value of each single risk feature, including 1q+. Patients and methods: The European Myeloma Network, within the HARMONY project, collected individual data from 10,843 patients with NDMM enrolled in 16 clinical trials. An additive scoring system on the basis of top features predicting progression-free survival (PFS) and overall survival (OS) was developed and validated. Results: In the training set (N = 7,072), at a median follow-up of 75 months, ISS, del(17p), lactate dehydrogenase, t(4;14), and 1q+ had the highest impact on PFS and OS. These variables were all simultaneously present in 2,226 patients. A value was assigned to each risk feature according to their OS impact (ISS-III 1.5, ISS-II 1, del(17p) 1, high lactate dehydrogenase 1, and 1q+ 0.5 points). Patients were stratified into four risk groups according to the total additive score: low (Second Revision of the International Staging System [R2-ISS]-I, 19.2%, 0 points), low-intermediate (II, 30.8%, 0.5-1 points), intermediate-high (III, 41.2%, 1.5-2.5 points), high (IV, 8.8%, 3-5 points). Median OS was not reached versus 109.2 versus 68.5 versus 37.9 months, and median PFS was 68 versus 45.5 versus 30.2 versus 19.9 months, respectively. The score was validated in an independent validation set (N = 3,771, of whom 1,214 were with complete data to calculate R2-ISS) maintaining its prognostic value. Conclusion: The R2-ISS is a simple prognostic staging system allowing a better stratification of patients with intermediate-risk NDMM. The additive nature of this score fosters its future implementation with new prognostic variables.

Second Revision of the International Staging System (R2-ISS) for Overall Survival in Multiple Myeloma: A European Myeloma Network (EMN) Report Within the HARMONY Project

D'Agostino, Mattia
First
;
Bonello, Francesca;Capra, Andrea;Gay, Francesca;Larocca, Alessandra;Boccadoro, Mario;
2022

Abstract

Purpose: Patients with newly diagnosed multiple myeloma (NDMM) show heterogeneous outcomes, and approximately 60% of them are at intermediate-risk according to the Revised International Staging system (R-ISS), the standard-of-care risk stratification model. Moreover, chromosome 1q gain/amplification (1q+) recently proved to be a poor prognostic factor. In this study, we revised the R-ISS by analyzing the additive value of each single risk feature, including 1q+. Patients and methods: The European Myeloma Network, within the HARMONY project, collected individual data from 10,843 patients with NDMM enrolled in 16 clinical trials. An additive scoring system on the basis of top features predicting progression-free survival (PFS) and overall survival (OS) was developed and validated. Results: In the training set (N = 7,072), at a median follow-up of 75 months, ISS, del(17p), lactate dehydrogenase, t(4;14), and 1q+ had the highest impact on PFS and OS. These variables were all simultaneously present in 2,226 patients. A value was assigned to each risk feature according to their OS impact (ISS-III 1.5, ISS-II 1, del(17p) 1, high lactate dehydrogenase 1, and 1q+ 0.5 points). Patients were stratified into four risk groups according to the total additive score: low (Second Revision of the International Staging System [R2-ISS]-I, 19.2%, 0 points), low-intermediate (II, 30.8%, 0.5-1 points), intermediate-high (III, 41.2%, 1.5-2.5 points), high (IV, 8.8%, 3-5 points). Median OS was not reached versus 109.2 versus 68.5 versus 37.9 months, and median PFS was 68 versus 45.5 versus 30.2 versus 19.9 months, respectively. The score was validated in an independent validation set (N = 3,771, of whom 1,214 were with complete data to calculate R2-ISS) maintaining its prognostic value. Conclusion: The R2-ISS is a simple prognostic staging system allowing a better stratification of patients with intermediate-risk NDMM. The additive nature of this score fosters its future implementation with new prognostic variables.
JCO2102614. Online ahead of print
JCO2102614
N/A
https://ascopubs.org/doi/full/10.1200/JCO.21.02614
https://doi.org/10.1200/jco.21.02614
D'Agostino, Mattia; Cairns, David A; Lahuerta, Juan José; Wester, Ruth; Bertsch, Uta; Waage, Anders; Zamagni, Elena; Mateos, María-Victoria; Dall'Olio, Daniele; van de Donk, Niels W C J; Jackson, Graham; Rocchi, Serena; Salwender, Hans; Bladé Creixenti, Joan; van der Holt, Bronno; Castellani, Gastone; Bonello, Francesca; Capra, Andrea; Mai, Elias K; Dürig, Jan; Gay, Francesca; Zweegman, Sonja; Cavo, Michele; Kaiser, Martin F; Goldschmidt, Hartmut; Hernández Rivas, Jesús María; Larocca, Alessandra; Cook, Gordon; San-Miguel, Jesús F; Boccadoro, Mario; Sonneveld, Pieter
File in questo prodotto:
File Dimensione Formato  
[Published Vsn] D'Agostino M et al - 2022 - JCO - R2-ISS - Article and Data Supplement.pdf

Accesso aperto

Descrizione: [Restricted access - Published Vsn. and Data Supplement] D'Agostino M et al. J Clin Oncol. 2022 May 23:JCO2102614. doi: 10.1200/JCO.21.02614. Epub ahead of print. PMID: 35605179. © 2022 by American Society of Clinical Oncology. Creative Commons Attribution Non-Commercial No Derivatives 4.0 License. Available at the following URL / disponibile all’URL: https://ascopubs.org/doi/full/10.1200/JCO.21.02614 | https://doi.org/10.1200/jco.21.02614
Tipo di file: PDF EDITORIALE
Dimensione 1.44 MB
Formato Adobe PDF
1.44 MB Adobe PDF Visualizza/Apri
[Author Vsn] D'Agostino M et al - 2022 - JCO - R2-ISS - post-print b.pdf

Accesso aperto

Descrizione: [Author Vsn. and Data Supplement] D'Agostino M et al. J Clin Oncol. 2022 May 23:JCO2102614. doi: 10.1200/JCO.21.02614. Epub ahead of print. PMID: 35605179. © 2022 by American Society of Clinical Oncology. Creative Commons Attribution Non-Commercial No Derivatives 4.0 License. The published version is available at the following URL / disponibile all’URL: https://ascopubs.org/doi/full/10.1200/JCO.21.02614 | https://doi.org/10.1200/jco.21.02614
Tipo di file: POSTPRINT (VERSIONE FINALE DELL’AUTORE)
Dimensione 2.21 MB
Formato Adobe PDF
2.21 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1862739
Citazioni
  • ???jsp.display-item.citation.pmc??? 2
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact