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Blood-based tests comparable to bone marrow biopsy for diagnosing, monitoring multiple myeloma
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Two methods of measuring multiple myeloma DNA in blood samples provided highly detailed genetic information that appeared consistent with results of bone marrow biopsy, according to research conducted at Dana-Farber Cancer Institute and Broad Institute of MIT and Harvard.
“Until now, we have not had a good way to measure how multiple myeloma cell populations evolve from precursor stages to diagnosed disease, and then respond to treatments,” Irene Ghobrial, MD, associate professor of medicine at Dana-Farber Cancer Institute, said in a press release. “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.”
HemOnc Today spoke with Ghobrial about how this research came about, the similarities between the results the two blood-based sampling methods yielded, their comparability with bone marrow biopsy results, and the potential implications if blood-based testing is proven feasible and effective.
Question: How did this research come about?
Answer: As with many other cancer types, we wanted to see if a blood biopsy would reflect what was happening in a bone marrow biopsy for patients with multiple myeloma. We know there is a clonal heterogeneity in the bone marrow and there are various clones in patients with multiple myeloma. However, the problem with bone marrow biopsy is that it takes only one piece of the bone marrow, and this does not truly reflect the entire tumor burden. There could be another area in bone marrow that has completely different clones that cause resistance, yet we do not know this because it is not the part we biopsied. We wanted to find out whether blood biopsy best reflects the entire tumor burden and tumor clone heterogeneity in a patient, and if it also can reflect what is happening in a bone marrow biopsy. We also wanted to see if we can use blood biopsy in the future, not only to replace bone marrow biopsy but to give a serial, sequential sample so we can understand design and exchanges that occur in a patients’ disease, either with regard to response to therapy, or progression from monoclonal gammopathy of undetermined significance or smoldering myeloma to overt disease.
Q: How did you conduct this research?
A: We worked very closely with Broad Institute, and we used a new technology developed there called ultralow pass whole-genome sequencing. By conducting this very easy and low-cost test, we can have a prognostic indication of whether a high tumor burden indicates more disease burden in the patient. It also can reflect whether we should conduct further testing, such as whole-genome sequencing or deeper targeted sequencing. We collected samples to examine the question of bone marrow or blood-based sampling. We then had a large sequential sample cohort of patients at different disease stages. This is a part of our effort at the Prevention of Progression Clinic at Dana-Farber, which we started a few years ago to focus on preventing progression of multiple myeloma.
Q: How did the two methods of blood-based sampling correlate with each other , and with bone marrow tests?
A: We examined circulating free DNA from 107 patients and circulating tumor cells from 56 patients. Gene profiles overlapped, demonstrating about 99% agreement between liquid and bone marrow biopsies for tumor gene mutations. Interestingly, we found that the bone marrow biopsy correlated very well with the blood biopsy. This was really fascinating, and we are now taking it to the next level of deeper sequencing to isolate circulating tumor cells.
Q: What are the potential implications if blood-based testing can be proven feasible and effective?
A: This would be great because, instead of the patient having to undergo a painful bone marrow biopsy — which cannot be done every week or every month — the blood biopsy allows all of the genomic information to be gathered easily, and it can be done without pain.
Q: What must be confirmed in future research?
A: We have to prove in a larger cohort that this indeed can replace bone marrow biopsy. We also want to see if we can do this in a lab, where we can deliver the information back to the patients, so we can show that this is not just research-level information. Third, we are trying to go much deeper to see if we can detect all mutations, even in a small fraction of tumor DNA, and to see if we can detect minimal residual disease.
Q: Is there anything else that you would like to mention?
A: This is an exciting time for us. Hopefully this can be something that we can deliver to our patients to make a difference in their prognosis and the treatment of their disease. – by Jennifer Southall
Reference:
Manier S, et al. Nat Commun. 2018;doi:10.1038/s41467-018-04001-5.
For more information:
Irene Ghobrial, MD, can be reached at Dana-Farber Cancer Institute, 450 Brookline
Ave., Boston, MA 02215; email: irene_ghobrial@dfci.harvard.edu.
Disclosure: Ghobrial reports no relevant financial disclosures.