News release

From: Adelaide University

Australian researchers have found a new biomarker for multiple myeloma that could help doctors rapidly identify patients at greatest risk of poor outcomes, enabling more personalised and effective treatments.

Multiple myeloma is an incurable cancer of plasma cells in the bone marrow and is the second most common blood cancer worldwide, with more than 188,000 new cases diagnosed each year.

Despite significant advances in treatment over the past two decades, most patients eventually relapse, and outcomes remain particularly poor for those with aggressive forms of the disease.

In a breakthrough study published in the British Journal of Haematology, Adelaide University and SA Pathology researchers have found that high levels of a protein called Desmoglein-2 (DSG2) are strongly associated with significantly shorter survival in patients with multiple myeloma.

The researchers analysed clinical and genomic data from 678 newly diagnosed patients and found that those with the highest levels of DSG2 faced substantially worse outcomes than patients with low levels of the protein.

Lead authors Professor Claudine Bonder, Dr Barbara McClure and Associate Professor Chung Hoow Kok, from Adelaide University's Centre for Cancer Biology, believe the discovery could help fill an important gap in current risk assessment.

"While genomic testing has improved our ability to identify high-risk disease, some patients who appear to have standard-risk myeloma still experience rapid progression and poor survival," Professor Bonder said.

"Our findings show that high DSG2 levels can identify patients with a particularly aggressive type of multiple myeloma that may not be captured by existing risk-stratification approaches."

The researchers found that patients with the highest DSG2 expression were linked to a significantly increased risk of both disease progression and death than those with the lowest expression levels.

The protein remained a strong predictor of patient outcomes even after accounting for age, disease stage, treatment type and stem cell transplantation.

The study also revealed that DSG2 may help identify patients whose disease is more dangerous than current classifications suggest.

Dr McClure said the findings suggest DSG2 testing could eventually complement existing risk-stratification screening used at diagnosis.

"Rapidly identifying patients who are likely to have more aggressive forms of the disease is critical because it can influence treatment decisions from the very beginning," Dr McClure said.

"DSG2 has the potential to become an additional tool that helps clinicians better predict how a patient's disease will behave and tailor treatment accordingly."

Researchers say further studies are now needed to validate the findings and investigate whether DSG2 itself could become a target for future therapies.

"If we can better understand the role DSG2 plays in disease progression, it may open the door to new precision medicine approaches to improve outcomes for myeloma patients with high-risk disease," Dr McClure said.

‘Elevated desmoglein-2 expression in multiple myeloma is a prognostic marker across genomic subtypes with impact on high-risk cytogenetics and a distinct gene expression profile’ is published in the British Journal of Haematology. DOI: https://doi.org/10.1111/bjh.70554