Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group
Antonio Palumbo1, Hervé Avet-Loiseau1, Stefania Oliva1
1Antonio 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, Rome; Elena Zamagni and Michele Cavo, Istituto di Ematologia Seragnoli, Università di Bologna, Bologna, Italy; Hervé Avet-Loiseau and Michel Attal, Institut Claudius Regaud, L'Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse; Thierry Facon, Service des Maladies du Sang, Hôpital Claude Huriez, Centre Hospitalier Regionale et Universitaire Lille, Lille; Philippe Moreau, University Hospital Hotel-Dieu, Nantes, France; Henk M. Lokhorst, VU University Medical Center, Amsterdam; Pieter Sonneveld, Erasmus MC, Rotterdam, the Netherlands; Hartmut Goldschmidt, University Hospital and National Center for Tumor Diseases Heidelberg, Heidelberg, Germany; Laura Rosinol, Hospital Clínic, Institut Clínic d'Investigacions Biomèdiques Ausgust Pi i Sunyer, Barcelona; Juan José Lahuerta, Hospital Universitario 12 de Octubre, Madrid; Jésus San Miguel, Clínica Universidad de Navarra, Centro de Investigaciones Médicas Aplicadas, IDISNA, Pamplona, Spain; Paul Richardson and Kenneth C. Anderson, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA; Shaji Kumar and S. Vincent Rajkumar, Mayo Clinic, Rochester, MN; Sagar Lonial, Winship Cancer Institute, Emory University, Atlanta, GA; Robert Z. Orlowski, The University of Texas MD Anderson Comprehensive Cancer Center, Houston, TX; Gareth Morgan, Myeloma Institutes for Research Therapy, University of Arkansas for Medical Sciences, Little Rock, AR; Brian G.M. Durie, Cedars-Sinai Comprehensive Canc
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.
