Improved survival outcomes and relative youthfulness of multiple myeloma patients with t(4;14) receiving novel agents are associated with poorer performance of the revised international staging system in a real aging society

The Revised International Staging System (R-ISS) was developed for a more accurate risk stratification of patients with symptomatic multiple myeloma (MM). However, original and subsequent validation studies of the R-ISS included relatively younger patients, many of whom were treated without bortezomib. Hence, we investigated the real-world prognostic performance of the R-ISS in 400 patients with MM treated with novel agents in Japan, an aging society. The patients had a median age of 72 years, and 96.0% were treated with bortezomib. Patients in R-ISS stage II were significantly older and failed to show significantly longer overall survival (OS) compared to patients in R-ISS stages III (median age; 74 and 70 years, respectively; P = 0.001, and median OS; 63.4 vs. 54.7 months, respectively; P = 0.32). However, OS differed significantly among patients with all conventional ISS stages. ISS stage III patients recategorized to R-ISS stage III were significantly younger than those recategorized to R-ISS stage II and had a relatively longer OS. As a reason for these findings, patients with the high-risk cytogenetic abnormality t(4;14) were significantly younger and had an improved OS compared to others, which can be attributed to a young age and bortezomib therapy, as previously suggested. In conclusion, the R-ISS was less successful than the ISS in discriminating between stages II and III among bortezomib-treated patients with MM in an aging society, which might be attributable to the inclusion of t(4;14) in the R-ISS categorization strategy.