The following is a summary of “In Multiple Myeloma, High-Risk Secondary Genetic Events Observed at Relapse Are Present From Diagnosis in Tiny, Undetectable Subclonal Populations,” published in the March 2023 issue of Oncology by Lannes, et al.

For a study, researchers sought to investigate how often high-risk copy number abnormalities (CNAs) were missed at diagnosis in patients with multiple myeloma (MM) and selected only at relapse. MM is a type of cancer characterized by CNAs, which can affect patient outcomes and are sometimes only observed during relapses, suggesting they were acquired during tumor evolution. The study utilized single-cell genomics to determine the frequency of these high-risk events being missed at diagnosis and selected at relapse.

About 81 patients with plasma cell dyscrasias were analyzed using single-cell CNA sequencing. 66 patients were selected at diagnosis, 9 at first relapse, and 6 in presymptomatic stages. A total of 956 newly diagnosed MM patients and those with first relapse MM were identified retrospectively with required cytogenetic data to evaluate the enrichment of CNA risk events and survival impact.

52,176 MM cells were analyzed, and 74 (91%) patients had 2-16 subclones. Among these patients, 28.7% had a subclone with high-risk features (del(17p), del(1p32), and 1q gain) at diagnosis. In addition, the study analyzed a patient with a subclonal 1q gain at diagnosis, postinduction, and first relapse samples, which showed a rise in the high-risk 1q gain subclone (16%, 70%, and 92%, respectively). Analysis of the clinical database showed that the frequency of 1q gain increased from 30.2% at diagnosis to 43.6% at relapse (odds ratio, 1.78; 95% CI, 1.58 to 2.00), suggesting that many patients had 1q gains at diagnosis in micro clones that were missed by bulk analyses. The study also found that the progression-free and overall survival curves were similar between patients who had the 1q gain from diagnosis and those who seemingly acquired it at relapse, indicating that more aggressive treatment may be necessary early on to prevent high-risk cells from becoming the dominant clone.

The study suggested that identifying scarce aggressive cells may require more aggressive treatment early on in the diagnosis to prevent them from becoming the dominant clone. The findings emphasized the importance of utilizing single-cell genomics in the diagnosis and treatment of MM patients.

Reference: ascopubs.org/doi/full/10.1200/JCO.21.01987