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Newly-diagnosed multiple myeloma patients may soon be able to look forward to better-targeted treatments

IMI project HARMONY is proposing a new, more accurate way of assessing the prognosis of patients with multiple myeloma.

19 September 2022
The image shows clusters of connected dots in different colours - red, yellow, green, blue, purple... Image by ElisaRiva via Pixabay
HARMONY used big data approaches to identify different subgroups within newly-diagnosed multiple myeloma patients who are currently classified as 'intermediate risk'. Image by ElisaRiva via Pixabay

The treatment - and outcome - of virtually all forms of cancer has improved immeasurably with advances in our scientific understanding of the disease. A considerable part of these improvements arise from being able to anticipate what will be the most effective treatment at the most appropriate time. Determining the extent to which a cancer is aggressive is known as ‘staging’. This is an important consideration in treatment decisions; an aggressive cancer may require a different and more intense treatment. The more accurate the staging, the higher the potential for a better outcome. Now, the IMI-funded HARMONY project may have identified an improved staging system for multiple myeloma, a common blood cancer.

Cancers are a complex group of diseases. Once the causes were poorly understood, and the available treatments were limited and frequently ineffective. However, as scientific and medical knowledge has advanced, many cancers that were once routinely considered terminal are now seen as treatable, manageable and sometimes even curable.

These advances have not come about only through better therapies; the emergence of earlier detection, more accurate diagnoses and better understanding of disease progression have all contributed. Indeed, the latter component is a vital consideration in determining the course of treatment; cancers have different degrees of malignancy, leading to a high or low risk of mortality. Therefore, high or low risk diseases require different treatment approaches.

Like many other cancers, the diagnosis and treatment of blood and lymphatic cancers has substantially improved in recent years, but there is still considerable scope for improvement. Now, researchers at the Innovative Medicines Initiative (IMI) project ‘HARMONY’ have proposed revising the current staging system for multiple myeloma, a common form of bone marrow cancer.

The HARMONY team unites more than 100 hospitals, research institutes, medical associations, patient organizations, pharmaceutical companies, regulatory agencies, and IT companies. They jointly aim to improve the care for people with haematological malignancies.

The project has built a unique data platform and has been conducting so-called ‘big data’ analyses, studying data from over 100 000 blood cancer patients. One of the HARMONY partners is the European Myeloma Network (EMN), which played a key role in this multiple myeloma project. Following an analysis of almost 11 000 newly-diagnosed multiple myeloma (NDMM) cases, the HARMONY multiple myeloma research team led by the EMN has discovered that a group of patients - previously classified as ‘intermediate risk’ are, in fact, much more diverse than originally thought. The proposed amendment seeks to redistribute this intermediate group by classifying multiple myeloma patients into four risk subgroups - low, low-intermediate, intermediate-high and high. 

The results have been published in the Journal of Clinical Oncology (JCO).

’Investigating data from 10 843 patients with NDMM, we discovered that patients who are currently classified as ‘intermediate-risk patients’ constitute a quite diverse group with varying risk of progression or death,’ explained HARMONY partner Mattia D’Agostino of the University of Turin, the first author of the paper.

‘In our paper in JCO, we propose a second revision of the International Staging System (R2-ISS) to improve the risk estimation in NDMM.’

The researchers conclude that the new staging system allows a better stratification of patients with intermediate-risk NDMM and that the additive nature of this score fosters its future implementation with new prognostic variables. The next step will be to apply this new staging system in clinical practice and to design the therapy tailored to the disease risk of the patient. This will facilitate better-informed treatment decisions for each subgroup, leading to better outcomes.

‘There are now so many drugs and combinations available that it is currently difficult to understand what the best treatment sequence is for individuals who have different age, disease characteristic, risk-factor, history of treatment response, physical condition etc.,’ explained Solène Clavreul of Myeloma Patients Europe.

’Having a new staging system that can facilitate treatment decision-making and better predict prognosis and response to treatment(s) can only benefit myeloma patients. We are looking forward to seeing it implemented in clinical practice. We are pleased to see the big data platform Harmony delivering tools for a more and more personalised healthcare, adapted to such complex disease which is myeloma. Better treatment sequences could reduce ‘trial and error' treatment approaches, save patients precious time, and improve their quality of life. We congratulate the team of researchers who performed this work and hope this will lead to better outcomes for patients.’

HARMONY is supported by the Innovative Medicines Initiative, a partnership between the European Union and the European pharmaceutical industry.