In multiple myeloma, different types of blood biopsies match up well with bone marrow tests

Bone marrow biopsies are the gold standard for diagnosing and monitoring the progression of multiple myeloma, but these procedures are far too invasive to perform at every patient visit. Scientists from the Dana-Farber Cancer Institute and the Broad Institute of MIT and Harvard, however, have shown that two ways to measure multiple myeloma DNA in blood samples provide highly detailed sets of genetic information that agree well not just with each other but with results from bone marrow tests.
“Until now, we haven’t had a good way to measure how multiple myeloma cell populations evolve from precursor stages to diagnosed disease, and then respond to treatments, says Irene Ghobrial, MD, a Dana-Farber medical oncologist. “This is where blood biopsies can make a huge difference—extending our understanding of multiple myeloma, and really giving us a timeline of how the disease progresses and responds to therapy.”
The collaborative research examined blood biopsies that gathered multiple myeloma tumour DNA from two sources. One is circulating free DNA (cfDNA), scraps of DNA released into the bloodstream by dying cells. The other is circulating tumour cells (CTCs)—myeloma cells themselves.
“Our discovery that cfDNA and CTC analyses agree with each other at the comprehensive level is an important finding, because this means that routine genetic profiling of patient tumours from blood would be feasible,” says Ghobrial, co-senior author on a paper reporting the work in Nature Communications.
The blood biopsy analyses followed a two-step sequencing approach, says Viktor Adalsteinsson, PhD, group leader of the Blood Biopsy Team at the Broad Institute and co-senior author on the paper. The first step, developed by his team and called “ultra-low pass” whole genome sequencing, was a cost-effective method to identify blood samples with tumour DNA fraction of at least 5-10%, allowing more comprehensive genetic analysis. In the second step, the researchers performed whole exome sequencing (analysing the protein-coding regions of the genome) on those samples.
The investigators examined cfDNA from 107 patients and CTCs from 56 patients. The scientists then matched up cfDNA with bone marrow data from nine patients, and compared all three forms of biopsy in four additional patients. Overall, the gene profiles overlapped closely—demonstrating about 99% agreement between liquid and bone marrow biopsies for tumour gene mutations, for instance.
Such high levels of agreement suggest that the two forms of liquid biopsy might be used interchangeably to track patients with multiple myeloma, the researchers say, and employing both techniques might further increase the chances of understanding the disease in each patient.

Dana-Farber Institutewww.dana-farber.org/newsroom/news-releases/2018/in-multiple-myeloma–different-types-of-blood-biopsies-match-up-well-with-bone-marrow-tests/