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COMy 2025 | The potential of using clonal plasma cell proportion in the S-phase as a prognostic marker for NDMM
Saurabh Zanwar, MD, MBBS, Mayo Clinic, Rochester, MN, discusses the potential of using clonal plasma cell proportion in the synthetic phase (S-phase) as a prognostic marker for newly diagnosed multiple myeloma (NDMM). He highlights that even within high-risk subgroups, an elevated S-phase can identify patients with inferior prognosis, and suggests that assessing this fraction can further refine risk stratification, which is crucial for risk-adapted therapy. This interview took place at the 11th World Congress on Controversies in Multiple Myeloma (COMy) congress in Paris, France.
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Transcript
Newly diagnosed myeloma is a very heterogeneous disease. We have very good data over decades now showing which cytogenetic abnormalities, which FISH abnormalities carry a high-risk connotation to them. But there is still this group of patients that have functionally high-risk disease, which we are not able to pick up with our current testing modalities.
The proportion of clonal plasma cells in the S-phase has consistently been shown to be an important prognostic marker...
Newly diagnosed myeloma is a very heterogeneous disease. We have very good data over decades now showing which cytogenetic abnormalities, which FISH abnormalities carry a high-risk connotation to them. But there is still this group of patients that have functionally high-risk disease, which we are not able to pick up with our current testing modalities.
The proportion of clonal plasma cells in the S-phase has consistently been shown to be an important prognostic marker. We recently identified that when the clonal fraction of more than 2% is in the S-phase, these patients tend to have markedly inferior prognosis. The median overall survival for this cohort was around four years compared to nine years in patients where the S-phase was less than 2%.
What was really interesting though was even within high-risk and ultra-high-risk subgroups like deletion 17p, two or more high-risk cytogenetics, 1q alterations, a high S-phase still was able to identify patients that performed worse. We also looked at the utility of an elevated S-phase in patients who had data available for the new IMS IMWG high-risk consensus stratification. And what we identified was even in patients with an IMS high-risk designation, if your S-phase was low, your survival outcome was actually fairly comparable to that of patients who did not have an elevated S-phase. And at the same time, if you had both the IMS IMWG high-risk designation, along with an elevated S-phase, the median survival was close to three years.
We feel that there is a utility for assessing the fraction of clonal plasma cells in the S-phase, and this can further refine the way we identify high-risk patients. This is going to be especially important as we transition into an era of risk-adapted therapy to have these nimble tools that we can assess fairly easily as part of our routine flow cytometry workup at diagnosis to give us a better idea of which patients might need more risk-adaptive therapy.
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