The novel MinimuMM-seq technique may make it possible to detect tumor cells in individuals at higher risk for multiple myeloma, assess the risk of disease progression in patients with myeloma, and track genetic changes in tumor cells over time from a single blood sample, according to a new study published by Dutta et al in Cancer Discovery.
Background
Multiple myeloma is often preceded by conditions that have no symptoms but are marked by the presence of the M protein. Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma are usually detected as a result of a routine blood test, but a formal diagnosis usually entails a bone marrow biopsy.
The MinimuMM-seq approach may have the potential to replace the bone marrow biopsy as the standard method of screening individuals for conditions that often precede myeloma and of determining the extent of the disease. Requiring only a blood draw, MinimuMM-seq may be less painful and less invasive for patients than a bone marrow biopsy.
"[A bone] marrow biopsy is used to fully characterize myeloma precursor conditions and, for patients with overt myeloma, to measure tumor burden and genetics—how advanced the disease is," explained first study coauthor, Ankit Dutta, PhD, a postdoctoral research fellow in the Department of Medical Oncology at the Dana-Farber Cancer Institute. "Tumor cells from the marrow are analyzed by fluorescence in situ hybridization [FISH] for the presence of certain genetic abnormalities. In this study, we asked whether MinimuMM-seq, which takes advantage of a variety of recent advances in cellular analysis, could be used to detect and genomically profile myeloma cells circulating in the blood for the same information."
In contrast to the FISH technique—which looks for a predetermined set of genetic abnormalities—MinimuMM-seq uses whole-genome sequencing to probe the entirety of the myeloma cells’ DNA and can therefore pick up abnormalities invisible to FISH.
Study Methods and Results
To determine if MinimuMM-seq could accomplish in circulating tumor cells what FISH was capable of in tumor cells from the bone marrow, investigators used the MinimuMM-seq technique to analyze circulating myeloma cells from 51 patients with myeloma or a precursor condition. For 24 of the patients who participated in the study, investigators also extracted bone marrow samples and biopsied them.
"We found that MinimuMM-seq was able to detect the same genetic abnormalities in circulating tumor cells that existed in bone marrow biopsy samples, including hallmark features of myeloma," highlighted first study coauthor Jean-Baptiste Alberge, PhD, a postdoctoral research fellow in the Department of Medicine at the Dana-Farber Cancer Institute.
For 8 patients, the investigators took blood samples on two separate occasions and tested the circulating tumor cells using MinimuMM-seq. "The genetic changes that occurred from the first set of samples to the second enabled us to track the shifting dynamics of the disease—how some genetic subtypes of tumor cells become more prevalent while others become less [prevalent] over time. We could also track the emergence of subtypes associated with more high-risk forms of myeloma," Dr. Alberge noted.
Conclusions
The findings suggested that MinimuMM-seq could be used to monitor the genetic course of the disease in patients and determine when changes in treatment are called for. "It can help us stratify patients by the risk level of their disease and get an early indication [of] when the disease is taking a turn for the worse," Dr. Dutta stressed. "And because MinimuMM-seq requires only a simple blood draw, it can be done regularly in a more patient-friendly manner for close monitoring compared to a bone marrow biopsy."
"The study offers a proof of concept of the utility of MinimuMM-seq for screening, early diagnosis, monitoring, and managing multiple myeloma in patients," concluded senior study author, Irene Ghobrial, MD, Professor of Medicine at Harvard Medical School and Director of the Clinical Investigator Research program in the Department of Medical Oncology at the Dana-Farber Cancer Institute.
Disclosure: The research in this study was supported by the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the National Institutes of Health, the International Myeloma Society, a Dana-Farber Cancer Institute Medical Oncology Grant Award, and Stand Up To Cancer. For full disclosures of the study authors, visit aacrjournals.org.
