Photo by Juan D. Alfonso
Analysis of circulating tumor cells (CTCs) can provide at least as much genetic information about multiple myeloma (MM) as a bone marrow (BM) biopsy, according to a new study.
Researchers found evidence to suggest that analyzing CTCs isolated from the peripheral blood of MM patients could help physicians monitor disease progression over time, track the emergence of drug resistance, and tailor therapies to individual patients.
Jens Lohr, MD, PhD, of the Broad Institute of MIT and Harvard in Cambridge, Massachusetts, and colleagues conducted this research and detailed their findings in Science Translational Medicine.
The researchers said they devised a method that was “highly sensitive” in detecting and sequencing single CTCs, even from patients with low tumor burden.
Specifically, the team found they could isolate CTCs from, and detect mutations in, blood samples from an MM patient who had achieved a very good partial response to treatment and a patient with monoclonal gammopathy of undetermined significance.
Overall, the researchers found that CTCs could be used to identify mutations relevant for prognosis, and some of these mutations were more abundant in CTCs than in BM samples.
For example, the team detected somatic mutations in the KRAS, BRAF, IRF4, and TP53 genes in single CTCs from 3 MM patients. And the same mutations were present in single BM-derived MM cells.
In another 3 patients, the proportion of CTCs harboring TP53 R273C, BRAF G469A, and NRAS G13D mutations was higher than that observed in BM-derived cells. In 2 of the patients, the mutations weren’t detectable in BM cells because of insufficient sample material.
The researchers also found that CTCs could reveal patients with an overabundance of molecules expressed by MM cells—such as CD38 and SLAMF7—that can be targeted by therapies currently approved to treat MM—such as daratumumab and elotuzumab.
The team therefore believes that, with further development, CTC analysis could be a valuable tool for advancing precision medicine in MM.
