Some smoldering myeloma patients may benefit from earlier treatment, says a new study by myeloma researcher Nikhil Munshi, MD, PhD at the Dana Farber Cancer Institute.
The standard course of treatment today in smoldering myeloma is to “watch and wait” for patients with standard risk disease and to encourage patients with high risk smoldering myeloma (defined by disease burden characteristics but not myeloma cell genetics) to obtain treatment within clinical trials. Some smoldering myeloma patients may never progress to active myeloma and myeloma specialists are hesitant to treat if a patient’s disease is unlikely to develop into active myeloma.
New findings in the study may warrant a different approach. The study was published in Nature Communications and included results from 11 patients who had their smoldering myeloma cells genetically tested by whole genome sequencing at a smoldering diagnosis and again at progression to active multiple myeloma.
The number of mutations increased at diagnosis in all but one patient, but was not overall significantly different from the SMM diagnosis. But the study showed a movement between mutations, suggesting that there is a dynamic competition during subclones during disease progression.
All 11 patients progressed to symptomatic multiple myeloma in a median of 8 months (range 2-41 months) independent of risk factors (m-protein levels, % of bone marrow involvement or cytogenetic features).
They divided the patients into two groups:
Static Progression Model (4 out of 10 patients): Where the disease genetic features or mutations stayed the same as patients progressed to active multiple myeloma. This suggested that the mutations were already present and progression just needed time to accumulate a sufficient disease burden before it became active myeloma. Median progression for this group was 5.5 months.
Spontaneous Evolution Model (6 out of 10 patients): Where a change in the myeloma cell genetics were observed as the disease transitioned from smoldering myeloma to active myeloma. Median time to progression for this group was 23 months.
“Our findings have provided important insights into the patterns of myeloma progression and into some of the mechanisms responsible for the genomic changes that occur as the disease advances,” Munshi remarks. “These results suggest that multiple myeloma needs to be redefined to include some patients with smoldering myeloma, and points the way to new treatment approaches geared to the course of disease development in each patient.”
In the future, a more accurate stratification of smoldering myeloma using disease genetic testing may more accurately stratify patients than today’s assessments of clinical features like number of bone lesions, anemia or renal issues. These tests could better identify patients with smoldering myeloma who already have the genetic mutations and could benefit from earlier treatment.