Is the Second Revision of the International Staging System (R2-ISS) for Multiple Myeloma Valid in a Real-World Population from China?

In 2022, the European Myeloma Network (EMN) proposed a new risk model by including 1q21+ defined as the Second Revision of International Staging System (R2-ISS). This new risk scoring system integrates the ISS stage, lactate dehydrogenase (LDH), 1q21+, del(17p), and t(4;14), and calculates the weighted risk score, resulting in four groups with significantly different survival. Considering the discrepancy in population features and therapeutic options of different regions, the aim of this study is to determine whether this new prognostic model is valid for MM patients under the real-world treatment pattern in China.

We performed a retrospective study on patients with NDMM, who were diagnosed and treated in our hospital between January 2013 to December 2019. To be eligible for analysis, we selected 505 NDMM patients with enough clinical data for the assignment of the R-ISS and the R2-ISS. All patients received proteasome inhibitors (PIs) or immunomodulatory drugs (IMiDs) -based treatment.

We firstly evaluated the impacts of 1q21+ and copy number variations on survival. The median PFS and OS of patients harbored with 1q21+ were 33.3 months and 62.6 months, respectively, both significantly shorter compared with others (PFS: 50.8 months, OS: not reached; P<0.001). Furthermore, patients with 1q21 gain experienced a comparable PFS to 1q21 amplification group (33.3 vs 30.7 months; P=0.707), and a similar result in OS (56.5 vs 62.6 months; P=0.574) was observed.

Based on the calculation of risk score in R2-ISS, 57 cases (11.3%) ranked as score 0 (R2-ISS I), 105 cases (20.8%) score 0.5-1 (R2-ISS II), 264 cases (52.3%) score 1.5-2.5 (R2-ISS III), and 79 cases (15.6%) score 3-5 (R2-ISS IV). The median OS was NR versus NR versus 63.8 versus 48.2 months, with the median PFS of 76.6 versus 64.3 versus 33.8 versus 30.7 months in the R2-ISS I, II, III, and IV groups, respectively. The survival differences among the four R2-ISS groups were statistically significant. Our results showed that 325 patients in R-ISS II group could be further divided into 82 cases (25.2%) R2-ISS II, 236 (72.6%) R2-ISS III, and 7 (2.2%) R2-ISS IV. And these newly classified patients got a statistically significant discrepancy in PFS and OS (P=0.01; P=0.003).

The R2-ISS system maintained its excellent performance for OS in the patients classified as PIs-based, IMiDs-based, PIs+IMiDs based, non-ASCT, young (≤65 years), and old (>65 years) groups. Surprisingly, the OS of patients receiving ASCT could not be well distinguished by the R2-ISS model (P=0.23). Further investigation found that all patients who received ASCT (n=163) experienced a considerable long survival, and the median OS was not reached at the last follow-up.

In conclusion, we confirmed that the new R2-ISS scoring model was a reliable and reproducible method to powerfully predict prognosis of MM patients in the real world. Our results also confirmed that the presence of 1q21+ confers poor outcomes but different copy numbers did not exert additional inferior impact, which provides robust proof for the revision of 1q21+ in the R2-ISS.