Revised international staging system for multiple myeloma: A report from international myeloma working group

Antonio Palumbo, Hervé Avet-Loiseau, Stefania Oliva, Henk M. Lokhorst, Hartmut Goldschmidt, Laura Rosinol, Paul Richardson, Simona Caltagirone, Juan José Lahuerta, Thierry Facon, Sara Bringhen, Francesca Gay, Michel Attal, Roberto Passera, Andrew Spencer, Massimo Offidani, Shaji Kumar, Pellegrino Musto, Sagar Lonial, Maria T. PetrucciRobert Z. Orlowski, Elena Zamagni, Gareth Morgan, Meletios A. Dimopoulos, Brian G.M. Durie, Kenneth C. Anderson, Pieter Sonneveld, Jésus San Miguel, Michele Cavo, S. Vincent Rajkumar, Philippe Moreau

Research output: Contribution to journalArticlepeer-review

757 Scopus citations


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 β2-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 β2-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.

Original languageEnglish (US)
Pages (from-to)2863-2869
Number of pages7
JournalJournal of Clinical Oncology
Issue number26
StatePublished - 2015

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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