29 Aug 2019

Monash researchers a step closer to myeloma blood test

by Anne Crawford

Prof. Andrew Spencer
A Monash University team has advanced its research into developing a novel blood test to detect multiple myeloma. The liquid biopsy test also has the potential in the future to give clinicians an indication of how a patient is responding to treatment.

The ACBD (Australian Centre for Blood Diseases) group, led by Professor Andrew Spencer, published its study recently in Leukemia.  

Multiple myeloma (MM), an incurable cancer of the plasma cells which are normally found in the bone marrow, affects more than 1900 Australians each year.

Professor Spencer said the liquid biopsy test is being developed as a more accurate, less invasive alternative to current bone marrow biopsy.

“There’s a massive amount of what’s called spatial heterogeneity in MM so it’s implausible that a bone marrow biopsy done at one site can accurately characterise the genome of the disease,” Professor Spencer said. “So our hypothesis is that if you analyse circulating cell-free DNA in plasma it will be representative of all the foci of myeloma in the body, whereas a single bone marrow biopsy can’t do that.”

The team has previously conducted proof of principle research that demonstrated the technique works, describing the mutated specimens from various patient groups using the approach. It draws on a biobank of liquid biopsies and marrows taken from patients in its investigatory clinical trials to conduct its studies.

The researchers looked at DNA, the more generally accepted target in this type of work,
and for the first time described the analysis of extracellular RNA, Professor Spencer said.

“What we showed in the DNA is that you can define the prognosis in the patient based on the number of mutations in the tumour burden using the liquid biopsy because the quantity of mutated DNA in the blood is a biomarker of this burden,” he said.

“We saw a very nice correlation between tumour burden defined by the liquid biopsy DNA quantity and patient outcome and also a correlation between the number of mutations in plasma and patient outcome – that’s the first time that’s been described in haematological malignancy,” he said.

The RNA part of the study specifically looked at the expression of genes that could hypothetically be modified by the drugs being used in patients, measuring the expression of these genes via the RNA in the plasma both at the start of the study and then on day five of the first week of treatment.

“We showed a very powerful correlation between changes in expression of some of those genes and the patients’ survival – up to a 10-fold difference in survival based on the changes in expression we saw,” Professor Spencer said.

“This is the first time this has been described,” he said.

The researchers will now try to validate the extracellular RNA analysis in a second sample set.

Professor Spencer said the approach may have potential as a tool for prognosis and also for changing a therapy early in the patient’s treatment if that was not working, enabling response-adaptive treatment.

“I think that in the future we won’t do bone marrow biopsies for multiple myeloma any more, just the blood test, and I think this lays the groundwork for that,” he said.

Professor Spencer said the RNA findings, while they need validating, were “provocative” because they challenged the accepted way of evaluating MM.

He said first author Dr Durga Mitraprabhu was instrumental in conducting the study.

To read more about the study please see the article below:

Mithraprabhu S, Morley R, Khong T, Kalff A, Bergin K, Hocking J, Savvidou I, Bowen KM, Ramachandran M, Choi K, Wong BKL, Reynolds J, Spencer A. Monitoring tumour burden and therapeutic response through analysis of circulating tumour DNA and extracellular RNA in multiple myeloma patients. Leukemia. 2019 Apr 16. doi: 10.1038/s41375-019-0469-x. [Epub ahead of print]

Two other recent studies on the liquid biopsy research:

Chen M, Mithraprabhu S, Ramachandran M, Choi K, Khong T, Spencer A. Utility of Circulating Cell-Free RNA Analysis for the Characterization of Global Transcriptome Profiles of Multiple Myeloma Patients. Cancers (Basel). 2019 Jun 25;11(6). pii: E887. doi: 10.3390/cancers11060887.

Mithraprabhu S, Hocking J, Ramachandran M, Choi K, Klarica D, Khong T, Reynolds J, Spencer A. DNA-Repair Gene Mutations Are Highly Prevalent in Circulating Tumour DNA from Multiple Myeloma Patients. Cancers (Basel). 2019 Jun 29;11(7). pii: E917. doi: 10.3390/cancers11070917.

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