Identifying High-Risk Genomic Predictors in Patients With Smoldering Multiple Myeloma
Posted: Thursday, August 13, 2020
Findings presented in the Journal of Clinical Oncology suggest that patients with smoldering multiple myeloma were more likely to develop multiple myeloma based on genomic predictors. The genomic analysis, performed by Irene M. Ghobrial, MD, of the Dana-Farber Cancer Institute, Boston, and colleagues, revealed that these abnormalities could distinguish patients who are at a high risk of progression toward multiple myeloma and, therefore, improve the precision of current clinical models.
“Ideally, our biological model could be combined with the traditional clinical models to get the best indication of a patient’s risk of progression,” the authors concluded. “Patients identified as being high risk could then be closely monitored for signs of advancing disease or participate in clinical trials of agents that aim to slow or stop progression.”
The authors used next-generation sequencing to study 214 patients with smoldering multiple myeloma. Whole-exome sequencing was performed on 166 tumors, including 5 tumors with serial samples, and deep-targeted sequencing on 48 tumors.
Dr. Ghobrial and colleagues found most of the genetic alterations that led to progression to multiple myeloma were already acquired by the time of diagnosis of smoldering multiple myeloma. Particularly, alterations of the mitogen-activated protein kinase pathway (KRAS and NRAS single nucleotide variants), the DNA repair pathway (deletion 17p, TP53, and ATM single nucleotide variants), and MYC (translocations or copy number variations) were all considered independent risk factors of disease progression after accounting for clinical risk staging.
The authors validated these findings in an external smoldering multiple myeloma cohort by revealing that patients who have any of these three alterations were more likely to progress to multiple myeloma. APOBEC-associated mutations, in particular, were enriched in patients who progressed to multiple myeloma and were associated with a shorter time to disease progression in their cohort.
Disclosure: For full disclosures of the study authors, visit ascopubs.org.
