Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group
Open accessAbstract
Purpose: The clinical outcome of multiple myeloma (MM) is heterogeneous. A simple and reliable tool is needed to stratify patients with MM. We combined the International Staging System (ISS) with chromosomal abnormalities (CA) detected by interphase fluorescent in situ hybridization after CD138 plasma cell purification and serum lactate dehydrogenase (LDH) to evaluate their prognostic value in newly diagnosed MM (NDMM). Patients and Methods: Clinical and laboratory data from 4,445 patients with NDMM enrolled onto 11 international trials were pooled together. The K-adaptive partitioning algorithm was used to define the most appropriate subgroups with homogeneous survival. Results: ISS, CA, and LDH data were simultaneously available in 3,060 of 4,445 patients. We defined the following three groups: revised ISS (R-ISS) I (n = 871), including ISS stage I (serum β 2 -microglobulin level < 3.5 mg/L and serum albumin level ≥ 3.5 g/dL), no high-risk CA [del(17p) and/or t(4;14) and/or t(14;16)], and normal LDH level (less than the upper limit of normal range); R-ISS III (n = 295), including ISS stage III (serum β 2 -microglobulin level > 5.5 mg/L) and high-risk CA or high LDH level; and R-ISS II (n = 1,894), including all the other possible combinations. At a median follow-up of 46 months, the 5-year OS rate was 82% in the R-ISS I, 62% in the R-ISS II, and 40% in the R-ISS III groups; the 5-year PFS rates were 55%, 36%, and 24%, respectively. Conclusion: The R-ISS is a simple and powerful prognostic staging system, and we recommend its use in future clinical studies to stratify patients with NDMM effectively with respect to the relative risk to their survival.
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The Revised International Staging System combines tumor burden and disease biology into a unified prognostic index.
“The Revised International Staging System (RISS) combines elements of tumor burden (ISS) and disease biology (presence of high risk cytogenetic abnormalities or elevated lactate dehydrogenase level) to create a unified prognostic index that and helps in clinical care as well as in comparison of clinical trial data (Table 4).55”
From Multiple myeloma: 2024 update on diagnosis, risk-stratification, and management (2024) · cites this paper as [55]
The RISS combines elements of tumor burden (ISS) and disease biology.
“The revised international staging system (RISS) combines elements of tumor burden (ISS) and disease biology [23].”
From Epidemiology, Staging, and Management of Multiple Myeloma (2021) · cites this paper as [23]
Patients with advanced disease stage (R-ISS stage III) have consistently shown poorer outcomes irrespective of the therapy received.
“Similarly, patients with advanced disease stage (R-ISS stage III) have consistently shown poorer outcomes irrespective of the therapy received4–6,19–22.”
From Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results (2023) · cites this paper as [21]
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- Authors
- Palumbo, A., Avet-Loiseau, H., Oliva, S., Lokhorst, H. M., Goldschmidt, H., Rosinol, L., Richardson, P., Caltagirone, S., Lahuerta, J. J., Facon, T., Bringhen, S., Gay, F., Attal, M., Passera, R., Spencer, A., Offidani, M., Kumar, S., Musto, P., Lonial, S., Petrucci, M. T., Orlowski, R. Z., Zamagni, E., Morgan, G., Dimopoulos, M. A., Durie, B. G. M., Anderson, K. C., Sonneveld, P., San Miguel, J., Cavo, M., Rajkumar, S. V., & Moreau, P.
- Affiliations
- Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT)
- Antonio Palumbo, Stefania Oliva, Simona Caltagirone, Sara Bringhen, and Francesca Gay, University of Torino, Azienda Ospedaliero-Universitaria Città della Salute della Salute e della Scienza di Torino; Roberto Passera, University of Torino, Torino; Massimo Offidani, Clinica di Ematologia, AUO Ospedali Riuniti di Ancona, Ancona; Pellegrino Musto, Istituto di Ricovero e Cura a Carattere Scientifico, Referral Cancer Center of Basilicata, Rionero in Vulture; Maria T. Petrucci, Sapienza University of Rome,...
- Mayo Clinic (US)
- Centre Hospitalier Universitaire de Nantes (FR)
- ORCID
- Palumbo, Antonio
- Oliva, Stefania
- Goldschmidt, Hartmut
- Richardson, Paul
- Lahuerta, Juan José
- Facon, Thierry
- Bringhen, Sara
- Gay, Francesca
- Attal, Michel
- Passera, Roberto
- Spencer, Andrew
- Offidani, Massimo
- Kumar, Shaji
- Musto, Pellegrino
- Lonial, Sagar
- Petrucci, Maria T.
- Orlowski, Robert Z.
- Zamagni, Elena
- Morgan, Gareth
- Dimopoulos, Meletios A.
- Durie, Brian G.M.
- Anderson, Kenneth C.
- Sonneveld, Pieter
- Rajkumar, S. Vincent
- Moreau, Philippe
- Venue
- Journal of Clinical Oncology
- Published
- 2015-09-10
- Volume
- 33
- Issue
- 26
- Pages
- 2863-2869
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- PMC
- PMC4846284
- OpenAlex
- W2128192762
- Semantic Scholar
- 08051e78ef41c5b4608415b5267eefaac45541bb
- Cited by
- 2,210
- References
- 32
- Citations by year
- 2026: 170 · 2025: 249 · 2024: 222 · 2023: 242 · 2022: 270 · 2021: 254 · 2020: 248 · 2019: 183 · 2018: 130 · 2017: 139 · 2016: 87 · 2015: 11
- FWCI
- 96.18
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Oncology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- Pure Amsterdam UMC (acceptedVersion, other-oa)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Amgen
- Bristol-Myers Squibb
- Sanofi
- Spectrum Pharmaceuticals
- Celgene
- Karyopharm Therapeutics
- Array BioPharma
- Genentech
- Chugai Pharmaceutical
- National Cancer Institute (U10CA180888, P50CA142509, U10CA032102, P50CA186781)
- Janssen Pharmaceuticals
- Cilag
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
- Keywords
- multiple myeloma, Revised International Staging System, prognostic staging, newly diagnosed multiple myeloma, chromosomal abnormalities, 17p deletion, lactate dehydrogenase, beta2-microglobulin, serum albumin, overall survival, progression-free survival, risk stratification
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Chromosome Aberrations, Female, Humans, L-Lactate Dehydrogenase, Male, Middle Aged, Multiple Myeloma, Neoplasm Staging, In Situ Hybridization, Fluorescence
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