An assessment of the Revised International Staging System using unselected patients with newly diagnosed and relapsed MM

On the 17^th February 2017 Tandon et al. from The Mayo Clinic, Rochester, USA, published an article in Blood which examined the benefits of using the Revised International Staging System (RISS) (for both newly diagnosed (ND) and relapsed/refractory (R/R) Multiple Myeloma (MM) patients) for improved prognosis and stratification into survival groups.  

Key Highlights

• Cohort 1 – NDMM patients:
  • Mean age of 65 years and 59.9% were male
  • Patients (1900) were recruited within 90 days of diagnosis from 2005 to 2015
  • Median follow-up of 5 years (95% CI; 4.8, 5.5 years)
  • OS and PFS was evaluated in a total of 1067 patients (P<0.0001):
    • RISS stage I - Median OS =10 years; Median PFS = 2.8 years
    • RISS stage II – Median OS = 6 years; Median PFS = 2.7 years
    • RISS stage III – Median OS = 2.6; Median PFS = 1.3 years
• Cohort 2 – RRMM patients:
  • Mean age of 65 years and 59.6% were male
  • 887 patients recruited from 23 clinical trials at the Mayo Clinic
  • Median follow-up was 2.3 years (interquartile range; 2.1, 2.6 years)
  • OS and PFS was evaluated in 456 patients (P<0.0001):
    • RISS stage I - Median OS = 4.3 years; Median PFS = 1.1 years
    • RISS stage II – Median OS = 2 years; Median PFS = 0.5 years
    • RISS stage III – Median OS = 0.8; Median PFS = 0.2 years

The authors also examined OS and PFS differences between patients diagnosed between 2005 and 2010, compared with those diagnosed between 2011 and 2015. They did observe some improvement in RISS between stages, but the difference was not statistically significant. The same variables used to determine RISS stage were given equal weight and used to generate a prognostic risk score for both cohorts. This also proved successful in stratifying patients with both NDMM and RRMM.

Conclusions

The RISS was devised using only data from patients enrolled in clinical trials and allows for an improved prognosis and better separation of patients (both NDMM and RRMM) into survival subgroups, by combining data from chromosomal abnormalities (CA) and serum lactate dehydrogenase (LDH), with ISS score. This scoring system also has clinical utility outside a clinical trial setting and could be used to classify patients for more customized treatment regimes.

Abstract

We analyzed the utility of Revised International staging system (RISS) in an unselected cohort of newly diagnosed multiple myeloma (NDMM; cohort 1), and relapsed/refractory multiple myeloma (RRMM; cohort 2) patients. Cohort 1 included 1900 patients seen within 90 days of diagnosis, from 2005 to 2015, while cohort 2 had 887 patients enrolled in 23 clinical trials at Mayo Clinic. The overall survival (OS) and progression-free survival (PFS) was calculated from the time since diagnosis or trial registration. The median estimated follow up was 5 and 2.3 years for Cohorts 1 and 2, respectively. Among 1067 patients evaluable in Cohort 1, the median OS and PFS was 10 and 2.8 years for RISS stage I, 6 and 2.7 years for RISS stage II and 2.6 and 1.3 years for RISS stage III (P<0.0001). Among 456 patients evaluable in Cohort 2, the median OS and PFS was 4.3 and 1.1 years for RISS stage I, 2 and 0.5 years for RISS stage II and 0.8 and 0.2 years for RISS stage III (P<0.0001). In conclusions, RISS gives a better differentiation of NDMM as well as RRMM patients into three survival subgroups and should be used to stratify patients in future clinical trials.