Evaluation of the Revised International Staging System in an independent cohort of unselected patients with multiple myeloma

Abstract

The Revised International Staging System (R-ISS) was recently introduced in order to improve risk stratification over that provided by the widely used standard International Staging System. In addition to the parameters of the standard system, the R-ISS incorporates the presence of chromosomal abnormalities detected by interphase fluorescence in situ hybridization [t(4;14), t(14;16) and del17p] and elevated serum lactate dehydrogenase. The R-ISS was formulated on the basis of a large dataset of selected patients who had participated in clinical trials and has not been validated in an independent cohort of unselected patients. Thus, we evaluated the R-ISS in 475 consecutive, unselected patients, treated in a single center. Our patients were older and more often had severe renal dysfunction than those in the original publication on the R-ISS. As regards distribution by group, 18% had R-ISS-1, 64.5% R-ISS-2 and 18% R-ISS-3. According to R-ISS group, the 5-year survival rate was 77%, 53% and 19% for R-ISS-1, -2 and -3, respectively (P<0.001). The R-ISS could identify three groups with distinct outcomes among patients treated with or without autologous stem cell transplantation, among those treated with either bortezomib-based or immunomodulatory drug-based primary therapy and in patients ≤65, 66-75 or >75 years. However, in patients with severe renal dysfunction the distinction between groups was less clear. In conclusion, our data in consecutive, unselected patients, with differences in the characteristics and treatment approaches compared to the original International Myeloma Working Group cohort, verified that R-ISS is a robust tool for risk stratification of newly diagnosed patients with symptomatic myeloma.

Figure 1.

Survival outcomes in 475 patients according to R-ISS group. (A) Progression-free survival (PFS) and (B) overall survival.

Figure 2.

Survival of patients of different age groups according to R-ISS stage. (A) Patients ≤65 years, (B) patients 66–75 years, and (C) patients ≥76 years.

Figure 3.

Survival according to the R-ISS for patients who did or did not receive ASCT and depending on first-line treatment regimen. (A) Patients treated with first-line regimens based on bortezomib (B) Patients treated with first-line regimens based on immunomodulatory drugs (IMID). (C) Patients who did not receive high-dose melphalan autologous stem cell transplantation (HDM-ASCT). (D) Patients who received HDM-ASCT.

Figure 4.

Overall survival according to R-ISS stage in patients categorized by renal fuction. (A) Patients with eGFR ≥30 mL/min/1.73 m². (B) Patients with eGFR <30 mL/min/1.73 m²