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High-Risk Secondary Events in Myeloma May Necessitate More Aggressive Treatment

By: Joshua Swore, PhD
Posted: Wednesday, March 1, 2023

Aggressively treating multiple myeloma as early as diagnosis may be required to prevent scarce cells from becoming the dominant clone, according to an article published in the Journal of Clinical Oncology. “Since certain copy number abnormalities are associated with a poor outcome, and assuming that they affect disease course, it would be clinically important to track the presence of these abnormalities in minor subclones from the time of diagnosis,” said Hervé Avet-Loiseau, MD, PhD, of the Institut Universitaire du Cancer de Toulouse-Oncopole, France, and colleagues. “Our study suggests that high-risk [copy number abnormalities] are not acquired after diagnosis but are present at diagnosis and selected by the treatment.”

The authors first analyzed 52,176 multiple myeloma cells from 81 patients via plasma cell dyscrasias and single-cell copy number abnormality sequencing. The group reported 74 patients had 2 to 16 subclones, with 28.7% possessing a high-risk subclone at diagnosis. They then took a closer look at the presence of the high-risk 1q subclone in patients at diagnosis, after induction, and at first relapse, finding a sequential rise in the high-risk factor (16%, 70%, and 92%, respectively).

The researchers next used a retrospective analysis to evaluate the prevalence of copy number abnormalities and their impact on survival. Cryogenic data from 956 patients with newly diagnosed and first-relapse multiple myeloma revealed that the presence of the 1q abnormality increased from 30.2% at diagnosis to 43.6% at relapse (odds ratio = 1.78; 95% confidence interval = 1.58 –2.00). Patients who acquired the 1q abnormality at diagnosis and those who acquired it at relapse demonstrated similar survival trajectories, indicating many patients had 1q gains that were missed by bulk analysis.

Disclosure: For full disclosures of the study authors, visit

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