Scoring System Could Guide Decisions in Transplant-Ineligible Myeloma

Researchers have developed and validated a clinical scoring system that could help guide treatment decisions among patients with multiple myeloma who are ineligible for transplantation.

The system, the UK Myeloma Research Alliance Risk Profile (MRP), used widely available clinical parameters, such as WHO performance status, International Staging System, age, and C-reactive protein (CRP) concentration, as prognostic variables. MRP was prognostic of overall survival in both internal and external validation studies. The study was published in Lancet Haematology.

“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 pre-emptive, upfront dose adjustments in patients with multiple myeloma, preventing toxicity and potentially enabling patients to stay on therapy for longer,” wrote Gordon Cook, PhD, of Leeds Institute of Cancer and Pathology at the University of Leeds in the United Kingdom, and colleagues.

According to the researchers, the parameters included in the MRP make it simpler to use than the International Myeloma Working Group (IMWG) Frailty Score, which is used to predict patient outcome but is considered to be lacking objectivity.

The researchers used data from the National Cancer Research Institute (NCRI) Myeloma XI study (1,852 patients) to internally validate the MRP, and from the Medical Research Council (MRC) Myeloma IX study to externally validate the system. MRP was prognostic of overall survival in both the NCRI-XI data (D-statistic, 0.840; 95% CI, 0.718–0.963) and the MCR-IX data (D-statistic, 0.654; 95% CI, 0.497–0.811).

The MRP classified patients as low, medium, or high risk. Each of the variables considered to be prognostic increased in severity across these three groups in both datasets. The risk groups were associated with overall survival and predicted early mortality in both studies as well.

The researchers noted that the MRP groups were prognostic in patients regardless of their exposure to different therapeutic combinations and in patients with genetic high-risk disease. Finally, MRP groups was also associated with the percentage of protocol dose delivered.

In an accompanying editorial, Sonja Zweegman, of Cancer Center Amsterdam, and Alessandra Larocca, of the University of Torino in Italy, wrote that this study is an important step toward creating an “easy-to-define prediction model for outcome and treatment feasibility.”

“Importantly, the prognostic value of this model was independent of treatment and cytogenetic risk profile,” they wrote. “Because these data are available in most studies, comparisons of the outcome of frail patients with different treatment regimens are now possible and could pave the way for frailty-adapted treatment.”

However, Zweegman and Larocca also noted that the score used by Cook and colleagues does not necessarily reflect frailty as originally defined because performance status is assessed by physicians and not patients.

“Unfortunately, the authors did not compare their score with the current gold standard, the IMWG frailty score,” they wrote. “Therefore, it is unknown whether both scores are equal in discriminating outcomes, and whether they identify an identical frail population who would benefit less from treatment.”