Photo by Juan D. Alfonso
Researchers from the International Myeloma Working Group (IMWG) have proposed revising the International Staging System (ISS) used to stratify patients with newly diagnosed multiple myeloma (MM).
The group’s revised ISS (R-ISS) combines the current ISS with tests for chromosomal abnormalities (CAs) and serum lactate dehydrogenase (LDH) in an attempt to refine the system’s prognostic value.
IMWG researchers assessed the R-ISS in more than 3000 newly diagnosed MM patients and found that patients with R-ISS stage I disease had better overall survival (OS) and progression-free survival (PFS) than patients with stage I disease according to the ISS.
And patients with R-ISS stage III disease had worse survival rates than patients with stage III disease according to the ISS. But PFS and OS numbers for stage II disease were the same with both systems.
The researchers reported these results in the Journal of Clinical Oncology.
They noted that the existing ISS relies on tests for serum β2-microglobulin and serum albumin to divide patients into 3 risk-factor stages. But the R-ISS adds interphase fluorescence in situ hybridization to check for CAs, along with separate tests for heightened LDH.
The researchers define the 3 R-ISS groups as follows:
- R-ISS I includes patients with ISS stage I disease (serum β2-microglobulin level < 3.5 mg/L and serum albumin level ≥ 3.5 g/dL), no high-risk CAs (del[17p] and/or t[4;14] and/or t[14;16]), and normal LDH levels (less than the upper limit of normal range).
- R-ISS III includes patients with ISS stage III disease (serum β2-microglobulin level > 5.5 mg/L) and high-risk CAs or high LDH levels.
- R-ISS II includes patients with all other possible combinations.
To evaluate the prognostic value of the R-ISS, the researchers analyzed data from 4445 newly diagnosed MM patients who were enrolled in 11 completed trials. ISS, CA, and LDH data were available for 3060 patients.
At a median follow-up of 46 months, the 5-year OS rate was 82% in the R-ISS I group (n=871), 62% in the R-ISS II group (n=1894), and 40% in the R-ISS III group (n=295). The 5-year PFS rates were 55%, 36%, and 24%, respectively.
In comparison, the 5-year OS rate was 77% for patients with ISS stage I disease (n=1615), 62% for ISS stage II (n=1630), and 47% for ISS stage III (n=987). The 5-year PFS rates were 49%, 36%, and 30%, respectively.
Based on this work, the researchers said the R-ISS is a simple but powerful prognostic staging system, and they recommend its use in future studies to stratify newly diagnosed MM patients effectively.
“The revised staging system can be used by doctors to discuss prognostic results very carefully with individual patients,” added Brian G.M. Durie, MD, chairman of the IMWG.
“It’s helpful to know the expectations and consider how treatments can be modified based on the new ISS system.”
