Validation of the R-ISS for stratification of transplant-eligible MM patients

The International Myeloma Working Group (IMWG) has developed a new Revised-International Staging System (R-ISS), which builds on the ISS by taking into account several additional factors (serum lactate dehydrogenase levels (LDH) and high-risk chromosomal abnormalities (CA)) in order to stratify multiple myeloma (MM) patients into three groups with varying outcomes.

Verónica González-Calle, from the Division of Hematology and Oncology Mayo Clinic, Scottsdale, USA, and colleagues, conducted a study to determine whether this new R-ISS risk model could be used to predict clinical outcomes (i.e. survival rate) in a cohort of newly diagnosed (ND) transplant-eligible MM patients. Their findings were published in the Annals of Hematology in April 2018.

Study design:

• A retrospective cohort of newly diagnosed NDMM transplant-eligible patients (pts), who had undergone autologous stem cell transplantation (ASCT), were studied
• Data were collected from January 2005–December 2014
• N = 134 (eligible pts required a complete dataset for ISS, LDH and CA)

Patient characteristics:

Table 1. Characteristics of transplant-eligible MM patients who underwent ASCT between 2004–2014

Key Findings:

• Median time from diagnosis to ASCT = 6.7 months (range 4–69 months)
• Median age at ASCT (years): ≤ 65 = 54; ≥ 65 = 80
• No of induction lines: 1 = 111 pts; ≥ 2 = 23 pts
• Median time to engraftment (days): for neutrophils = 11 (5–19) and platelets = 17 (7–34); only one case of graft failure
• Median follow-up = 59.6 months (7.3–135.4)
• Death = 41 pts; died or progressed after ASCT = 93 pts
• Results according to ISS classification:
  • Median OS: High-risk CA vs standard-risk CA = 57.4 months vs not reached (NR) (P = 0.001)
  • Patients with high LDH levels vs normal LDH levels = 36.1 vs NR (P < 0.001)
• Results based on the R-ISS classification (R-ISS I vs R-ISS II vs R-ISS III):
  • Overall survival (OS) from ASCT (months) = NR vs 110.9 vs 37.2; P = 0.0001
  • Probability for 5-year OS (%) = 86 vs 68 vs 28
  • Progression-free survival (PFS) (months) = 35.2 vs 36.1 vs 19.2 (P = 0.005)
• The impact of high-risk CA on R-ISS II was assessed by re-classifying into: R-ISS IIa = not group I or III and lack of high risk CA and R-ISS IIb = not R-ISS group I or III and presence of high-risk CA:
  • Median OS (R-ISS I vs R-ISS IIa vs R-ISS IIb vs R-ISS III) = NR vs 110.9 vs 69.8 vs 37.2; P < 0.001
  • Median PFS (R-ISS I vs R-ISS IIa vs R-ISS IIb) = 35.2 vs 48.2 vs 32.9; P = 0.06
• Identification of additional risk factors for OS:
  • OS for pts with renal impairment = 37.2 months; P < 0.001
  • OS for pts with ≥ 2 lines of induction treatment; P = 0.005
• Increase in hazard ratio (HR) for OS:
  • Between R-ISS III and R-ISS I = 6.9 (95%CI; 2.4–20.3; P = 0.001)
  • Between R-ISS II and R-ISS I = 1.5 (95%CI; 0.6–3.6)
  • Between after and before ASCT in pts who received ≥ 2 lines of induction = 3.8 (95%CI, 1.7–8.5; P = 0.001)

The reclassification of MM patients who underwent ASCT at diagnosis showed that R-ISS was an independent and reliable predictor for OS after ASCT. There was a significantly shorter OS in patients classified as R-ISS IIb in comparison to patients classified as R-ISS IIa. It was concluded that the R-ISS can improve the risk-stratification of transplant-eligible MM patients in terms of predicting OS rates. In turn, this information can help to guide more effective treatment decisions.