Heterogeneity in long-term outcomes for patients with Revised International Staging System stage II, newly diagnosed multiple myeloma

Abstract

In the era of personalized treatment in multiple myeloma, high-risk patients must be accurately defined. The International Myeloma Working Group recommends using the Revised International Staging System (R-ISS) to identify high-risk patients. The main purpose of our work was to explore the heterogeneity of outcome among R-ISS stage II patients assessing the impact of ISS, chromosomal abnormalities (CA) and LDH level in this subgroup. Data were issued from 1,343 newly diagnosed myeloma patients up to 65 years, enrolled in 3 clinical trials implemented by the Intergroupe Francophone du Myelome. All patients were eligible to an intensive treatment. Patients R-ISS stage II but ISS stage I had 1.6 times more risk of death than patients R-ISS stage I (adjusted HR 1.6; 95% CI, 1.1 to 2.2; P = .01) and patients R-ISS stage II but ISS stage III had a better overall survival than patients R-ISS stage III (adjusted HR 0.7; 95% CI, 0.4 to 0.9, P = .02). However, among patients classified in R-ISS II, ISS stage and CA (del(17p) and t(4;14)) were still relevant prognostic factors for death. Dividing R-ISS stage II into 3 subgroups: ISS I with standard risk CA, ISS II or III with standard risk CA and, high risk CA patients, median overall survivals were respectively not reached, 112 and 71 months (P < 0.001). In conclusion, stratification of patients in the R-ISS stage II group can be improved by taking into account CA and ISS. However, this does not improve predictive performance of survival models.

Analysis of High-Risk Extramedullary Relapse Factors in Newly Diagnosed MM Patients

“…However, the 3-year extramedullary relapse rates of high-risk patients with the extramedullary relapse prediction score established by us are as high as 76%, which has a better ability to predict extramedullary relapse than the existing ISS stage and R-ISS stage. Accurate survival prediction is important because prognostic factors influence treatment choice [ 35 ]. Early identification of patients with high-risk extramedullary relapse and taking active treatment measures to prevent the emergence of extramedullary relapse in clinical practice is of great significance for improving the prognosis of NDMM patients.…”

Liquid biopsy by analysis of circulating myeloma cells and cell-free nucleic acids: a novel noninvasive approach of disease evaluation in multiple myeloma

“…The ISS is the most reliable staging system in MM, and CA was integrated into the R-ISS. However, great heterogeneity in clinical characteristics and outcomes was observed in cases within identical R-ISS risk groups, particularly in the R-ISS II group [82][83][84], indicating the need for new parameters. Several studies presented in Table 3 have confirmed that the presence and quantification of CMMCs further improved the risk stratification of patients with different prognosis in the identical ISS and R-ISS stages [6,19,22,28,34,68,71].…”

Current Main Topics in Multiple Myeloma

“…Despite the application of validated risk stratification systems, the category of intermediate risk MM now includes a very heterogeneous group of patients [ 6 ], characterized by vastly different prognoses, opening the challenge to build a more exhaustive risk stratification model [ 7 ].…”