The Revised International Staging System (R-ISS) and the International Myeloma Working Group 2014 (IMWG 2014) are newer staging systems used to prognosticate multiple myeloma (MM) outcomes. We hypothesized that these would provide better prognostic differentiation for newly diagnosed multiple myeloma (MM) compared with ISS. We analyzed the Center for International Blood and Marrow Transplant Research database from 2008 to 2014 to compare the 3 systems (N = 628) among newly diagnosed MM patients undergoing upfront autologous hematopoietic cell transplantation (AHCT). The median follow-up of survivors was 48 (range, 3 to 99) months. The R-ISS provided the greatest differentiation between survival curves for each stage (for overall survival [OS], the differentiation was 1.74 using the R-ISS, 1.58 using ISS, and 1.60 using the IMWG 2014) . Univariate analyses at 3 years for OS showed R-ISS I at 88% (95% confidence interval [CI], 83% to 93%), II at 75% (95% CI, 70% to 80%), and III at 56% (95% CI, 3% to 69%; P < .001). An integrated Brier score function demonstrated the R-ISS had the best prediction for PFS, though all systems had similar prediction for OS. Among available systems, the R-ISS is the most optimal among available prognostic tools for newly diagnosed MM undergoing AHCT. We recommend that serum lactate dehydrogenase and cytogenetic data be performed on every MM patient at diagnosis to allow accurate prognostication.
Based on ISS (n ISS I/ II/ III = 48/ 92/ 46) and SKY92, 186 patients were classed into four risk groups: SKY92 high-risk combined with any ISS stage (13%), SKY92 standard-risk and ISS III (21%), SKY92 standard-risk and ISS II (45%) and SKY92 standard risk and ISS I (21%; Kuiper et al., 2015; Blood, 126: 1996 Blood, 126: -2004. The median PFS of these respective groups was 11, 21, 22 and 25 months and the median OS was 18, 49, 56 and 88 mo (PFS: LR p-value = 5x10 -3 ; OS: LR p-value = 2x10 -4 ). Classifying in R-ISS stages (n R-ISS I/II/III = 12/129/28) demonstrated a median PFS of 13, 20 and 30 months (LR p-value = 5x10 -3 ) and a median OS of 25, 54 and 78 months (LR p-value = 1x10 -3 ). Factors independently associated with OS in the multivariate analysis were SKY92-ISS, R-ISS and del17p, whereas only SKY92-ISS and R-ISS remained independently associated with PFS. Eleven SKY92 high-risk patients were treated with lenalidomide and demonstrated a median OS of 55 months compared to 17 months for thalidomide treated high-risk patients (n = 15). The median OS in standard-risk patients was 59 months (lenalidomide) vs 61 months (thalidomide). Using an interaction term in the Cox regression model, a significant difference in OS (p = 0.04) was found between the treatment arms conditional on SKY92 risk status. Summary/Conclusion: Also in non-transplant eligible MM patients, the SKY92 classifier is a robust marker to identify high-risk patients. The SKY92-ISS has prognostic value independent of the revised ISS. In addition, SKY92 high-risk patients appear to have a survival benefit of lenalidomide treatment over thalidomide treatment, which is not found for SKY92 standard risk patients.
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