Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group

AA Palumbo, H Avet-Loiseau, S Oliva, HM Lokhorst, H Goldschmidt, L Rosinol, P Richardson, S Caltagirone, JJ Lahuerta, T Facon, S Bringhen, F Gay, M Attal, R Passera, A Spencer, M Offidani, S Kumar, P Musto, S Lonial, MT PetrucciRZ Orlowski, E Zamagni, G Morgan, MA Dimopoulos, BGM Durie, KC Anderson, Pieter Sonneveld, JS Miguel, M Cavo, SV Rajkumar, P Moreau

Research output: Contribution to journalArticleAcademicpeer-review

1420 Citations (Scopus)


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 beta(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 beta(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. (C) 2015 by American Society of Clinical Oncology
Original languageUndefined/Unknown
Pages (from-to)2863-+
JournalJournal of Clinical Oncology
Issue number26
Publication statusPublished - 2015

Research programs

  • EMC MM-02-41-03

Cite this