The Discriminatory Ability of the R-ISS Is Equivalent to the ISS in a Large Cohort of Newly Diagnosed Multiple Myeloma (NDMM) Patients

Background In the era of personalized treatment in multiple myeloma, high-risk (HR) patients must be defined accurately more than ever. The International Myeloma Working Group (IMWG) recommends to use the Revised International Staging System (R-ISS) to identify HR patients. This score combines ISS, abnormal serum LDH level and 3 high risk chromosomal abnormalities (CA): del(17p), t(4;14) and t(14;16). However, with the advent of new tools in genomics, assessing only 3 abnormalities seems to be limited. Moreover, LDH level is impacted by various medical conditions; its relevance in the score is questionable. Aims The main purpose of our work was to assess the R-ISS on a multi-center cohort of transplant-eligible patients (1180 patients). To our knowledge, this is the first large scale study in Europe. Methods Data were collected from NDMM patients enrolled in 3 clinical trials implemented by the Intergroupe Francophone du Myélome. All patients were eligible to an intensive treatment. The overall survival (OS) and progression-free survival (PFS) curves were estimated using the Kaplan-Meier method and compared using the stratified log-rank test. The hazard ratio (HR) for progression or death were estimated by a multivariate Cox regression analysis adjusted for age, sex and therapy. Discrimination was assessed by the Harrell's concordance index (C-index) which estimates the proportion of all pairs of patients in whom prediction and outcome are concordant and takes values from 0.5 (no discrimination) to 1.0 (perfect discrimination). Results Altogether, 1180 patients with MM were analysed. Median age of our cohort was 58 years. The majority of patients (78%) received an intensive treatment followed by an autologous stem-cell transplantation (ASCT). Median follow-up was 94 months for OS. Forty-three percent of patients had ISS stage I, 39% had ISS stage II and 18% had ISS stage III. In the multivariable Cox model, the risk of death was increased for ISS stage II versus I (HR, 1.8; P < 0.001), as well for R-ISS stage III versus I (HR, 2.1; P < 0.001). Thirty percent of patients had R-ISS stage I, 62% had R-ISS stage II and 8% had R-ISS stage III. In the multivariable Cox model, the risk of death was 1.8 times higher for R-ISS stage II versus I and 3.0 times higher for R-ISS stage III versus I. Then we compared patients between their couple ISS/R-ISS. Thirty-one percent of the patients from ISS I were upgraded in R-ISS II; 55% of ISS III patients were reclassified