Using models to measure the progression risk of patients with monoclonal gammopathy of undetermined significance (MGUS) over time improves the assessment of risk of progression to smoldering multiple myeloma and multiple myeloma, according to findings published in Blood Cancer Journal.
The retrospective study by a research group in Germany shows the value of regular MGUS measuring, which has become the regular practice of clinicians managing patients with MGUS, said author Elias K. Mai, MD, of Heidelberg University Hospital in Germany.
“Our results demonstrate that the individual risk of progression is optimized after repeated risk assessments over time,” he said. “We further show that most of the patients remain in their risk group assigned at baseline, regardless of the applied risk model. Patients who migrate to a higher risk group over time should be considered to have a higher risk of progression. Thus, this should prompt more frequent monitoring in clinical routine.”
The study included 427 patients with MGUS that was diagnosed using the current 2014 International Myeloma Working Group criteria at Heidelberg University Hospital between 2005 and 2023.
For the 183 patients who had at least one follow-up using the Mayo2005 risk model, 40 patients migrated to a higher-risk group, 20 to a lower-risk group, and nine migrated between different risk groups, while most (n=114) remained in their baseline risk group.
The pattern for those with follow-up using the Sweden2014 model was similar: of 157 patients, 43 migrated to a higher-risk group, 18 to a lower-risk group, 10 switched around several times, and 86 stayed in their original risk group.
There was less migration group-to-group for those with follow-up under the NCI2019 model, with 136 of 162 remaining in their initial risk group, 21 moving to a higher-risk group, and three moving to a lower-risk group.
Upstaging to a higher-risk category was associated with an increased risk of progression, compared to those who remained stable in the low-risk categories, researchers found. For those assessed with the Mayo2005 model, the hazard ratio (HR) was 5.43 (95% CI 1.21-24.39; p=0.027). For the Sweden2014 model, the HR was 13.02 (95% CI 5.25-32.28; p<0.001). Using the NCI2019 model, the HR was 5.85 (95% CI 2.49-13.74; p<0.001).
“Clinicians should monitor MGUS repeatedly over time to detect disease progression to multiple myeloma or a plasma cell disorder requiring treatment,” Dr. Mai said.
At his center, their clinical practice for follow-up of patients with MGUS follows the current European Myeloma Network and the International Myeloma Working Group recommendations, which suggest that patients should be risk stratified and that their follow-up should be aligned according to their individual risk of progression.
“Follow-up visits may therefore vary in time for individual patients, for example, every six to 12 months,” Dr. Mai said.
Even though the findings are retrospective and come from a single academic center, he said, they are a step forward in that they provide proof that regularly assessing risk gives vital information for managing patients with MGUS.
“To our knowledge, the value of longitudinal reassessment applying the three major staging models for MGUS beyond baseline has not been shown previously,” he said. “Our analysis comprised more than 400 patients, and our findings are robust. We therefore feel confident that our findings are of substantial clinical importance for the improvement of the surveillance of patients with MGUS. However, the median follow-up of the cohort was relatively short, with approximately three years with a maximum follow-up of eight years. Thus, confirmation of our results with a longer follow-up and different patient cohort — for example, from other or multiple clinical centers — is desirable.”
Any conflicts of interest declared by the authors can be found in the original article.
Reference
Zuern K, Hielscher T, Werly A, et al. Longitudinal assessment of established risk stratification models in patients with monoclonal gammopathy of undetermined significance. Blood Cancer J. 2024;14(1):148.
