A single tool that combines the International Staging System (ISS) with testing for chromosomal abnormalities (CA) and serum lactate dehydrogenase (LDH) affords a superior staging system for multiple myeloma, according to a study published in the Journal of Clinical Oncology.
The new staging system, called R-ISS, was able to identify three survival patterns in patients with newly diagnosed multiple myeloma:
Dr. Antonio Palumbo
• The first, R-ISS I (n = 871), included ISS stage I (serum 2-microglobulin level less than 3.5 mg/L and serum albumin level of 3.5 g/dL or more), no high-risk chromosomal abnormalities [del(17p) and/or t(4;14) and/or t(14;16)], and normal serum lactate dehydrogenase level (less than the upper limit of normal range).
• R-ISS III (n = 295) included ISS stage III (serum-beta-2-microglobulin level greater than 5.5 mg/L) and high-risk chromosomal abnormalities or high serum lactate dehydrogenase level.
• R-ISS II (n = 1,894) included all other possible combinations.
Corresponding rates of 5-year overall survival were 82% for R-ISS stage I, 62% for R-ISS stage II, and 40% for R-ISS stage III at a median follow-up of 46 months. The 5-year progression-free survival rates were 55%, 36%, and 24%, respectively.
Multiple myeloma “can no longer be considered a single disease, but a mix of different disease entities,” wrote Dr. Antonio Palumbo, chief of the myeloma unit in the department of oncology, division of hematology, University of Torino (Italy) and his colleagues (J Clin Oncol. 2015 Aug 3. doi: 10.1200/JCO.2015.61.2267).
“The combination of three different prognostic tools in the R-ISS allows a better evaluation of patient prognosis; approximately 26% of patients would have been wrongly allocated to a good-prognosis group if we had considered only one of these three factors,” the authors emphasized.
“In clinical practice, a better definition of [multiple myeloma] subgroups is essential to provide more effective personalized therapies,” they said. “The R-ISS staging system is a new risk stratification algorithm with an improved prognostic power compared with the individual ISS, CA, and LDH parameters.”
The individual roles of the three predictors in R-ISS were initially evaluated in a population of 4,445 patients with newly diagnosed multiple myeloma who were enrolled in 11 international, multicenter clinical trials from 2005 to 2012. The authors used the K-adaptive partitioning algorithm to define the most appropriate subgroups in 3,060 patients who had complete ISS, CA, and LDH data.
Subgroup analyses for overall survival and progression-free survival also were conducted. The risk of death was higher for patients older than 65 years (hazard ratio, 1.32; 95% confidence interval, 1.14-1.52; P <.001), male sex (HR, 1.16; 95% CI, 1.02-1.33; P = .029), R-ISS stage II versus I (HR, 3.59; 95% CI, 2.68-4.80; P <.001), and R-ISS stage III versus I (HR, 9.64; 95% CI, 6.24-14.88; P <.001).
The risk of progression also was higher for those older than 65 years (HR, 1.57; 95% CI, 1.42-1.75; P <.001), R-ISS stage II versus I (HR, 1.99; 95% CI, 1.61-2.37; P <.001), and R-ISS stage III versus I (HR, 3.37; 95% CI, 2.54-4.56; P <.001).
Almost all (95%) of the patients received novel agents, and these therapies improved overall survival across prognostic subgroups.
There is no disclosure of outside funding for this study. Several of the coauthors have disclosed financial relationships with industry, as noted in the paper.