A proposed clinical scoring system using readily available laboratory data, rather than complex formulas, can be used to predict risk for overall survival and help with clinical decision making for patients with multiple myeloma who are ineligible for stem cell transplants, the system’s creators claim.
Peter Anderson/ Pathology Education Informational Resource Digital Library/copyright University of Alabama at Birmingham, Department of Pathology
When applied to data from two clinical trials that enrolled patients with transplant-ineligible multiple myeloma, the UK Myeloma Research Alliance Risk Profile (MRP) was shown to accurately group patients into low-, medium- and high-risk categories and was prognostic of overall survival, reported Gordon Cook, PhD, of the University of Leeds, England, and his colleagues.
“The ability of clinical scoring systems, such as that proposed here, to predict whether a patient is likely to stop treatment early because of treatment intolerability, could enable preemptive, upfront dose adjustments in patients with multiple myeloma, preventing toxicity and potentially enabling patients to stay on therapy for longer,” they wrote in the Lancet Haematology.
The investigators used data on 1,852 newly diagnosed patients recruited to the non–intensive treatment pathway of the UK’s National Cancer Research Institute Myeloma XI study (NCRI-XI, ISRCTN49407852) for a training dataset and internal validation dataset, and 520 patients recruited into the Medical Research Council Myeloma IX study (MRC-IX, ISRCTN68454111) for the test dataset.
Patient characteristics, biochemical measurements, and hematological data were plugged into univariate and multivariate models to determine their potential as prognostic variables.
The final model for the test and validation datasets included World Health Organization performance status, the multiple myeloma International Staging System, patient age, and C-reactive protein concentrations.
As noted before, the scoring algorithm groups patients into low-, medium- and high-risk categories, with each of the prognostic variables increasing in severity across the three groups in both clinical trials.
In the NCRI-XI trial, median overall survival for patients in the MRP low-risk group was 60 months, compared with 44 months in the medium-risk group, and 25 months in the high-risk group.
Similarly, in the MRC-IX trial, the respective median overall survival was 49, 34, and 20 months.
The risk groups also were associated with progression-free survival in each trial, although not as robustly as the association with overall survival.
The investigators also found that, the higher the risk group, the greater the likelihood that the median percentage of protocol dose delivered would be lower, and both a decrease in protocol dose delivered and quality of life at baseline were associated with increased risk.
The MRP categories were prognostic in patients treated with various therapeutic regimens and in patients with high-risk cytogenetics.
“None of the risk scoring systems previously developed in myeloma are dynamic, making them unable to accommodate changes in disease-related frailty that might be minimized by effective anti-myeloma therapy. There is therefore scope to improve clinical risk scores by the addition of a suitable frailty biomarker, which is currently still in developmental stages,” Dr. Cook and his colleagues wrote.
The study was funded by the Medical Research Council, Novartis, Schering Health Care, Chugai, Pharmion, Celgene, Ortho Biotech, Cancer Research UK, Celgene, Merck Sharp & Dohme, and Amgen. Dr. Cook reported grants and nonfinancial support from Celgene, Amgen, and Merck Sharp & Dohme, during the conduct of the study and personal fees from other companies outside the submitted work.
SOURCE: Cook G et al. Lancet Haematol. 2019 Mar;6(3):e154-66.