The Horizon 2020 MMpredict initiative was started on November 1st 2016 and included the following consortium partners: SkylineDx B.V., the Department of Haematology of the Erasmus University Medical Centre Rotterdam (Erasmus MC), the Department of Onco-Haematology of the University of Turin (UNITO), the Institute for Medical Technology Assessment of the Erasmus University Rotterdam (EUR) and the Myeloma Patients Europe AISBL (MPE), combining a small to medium-sized enterprise specialised in molecular diagnostics, two clinical centres with world renowned key opinion leaders, a leading health economic institute, and a European Multiple Myeloma patient advocacy organisation. The consortium aims to develop and commercialize a personalised medicine tool that is capable of predicting the most effective treatment strategy for individual Multiple Myeloma patients.

Multiple Myeloma (MM) is an incurable disease of the patients’ plasma cells, which are specialized white blood cells located within the interior of larger bones. Here, embedded in soft, spongy tissue – also known as bone marrow – they produce and secrete antibodies as part of the immune system, for the neutralization of pathogens. This type of blood cancer is characterized by excessive numbers of abnormal plasma cells that crowd out remaining, healthy cells. Despite the fact that MM is a very heterogeneous disease it affects the body in several ways resulting in symptoms like anaemia, bone lesions, infections, hypercalcemia, fatigue, and pain. In Europe, each year around 40.000 new MM cases are diagnosed. MM is the second most common form of blood cancer with an average 5-year survival of approximately 50%. The disease is treatable, but unfortunately remains currently incurable. In recent years the treatment landscape of MM has evolved considerably, resulting in major improvement of overall survival. Despite the progress, not all individuals seem to benefit equally. Due to large tumour heterogeneity and patient’s intrinsic characteristics (like; age and fitness), different clinical outcomes are observed within the MM population. Moreover, while MM treatment options are expanding, their efficient implementation remains mainly based on trial-and-error. As a result, patients may receive one or even multiple ineffective treatments before switching to an effective alternative. Since cancer treatments are in general very toxic, this will often be associated with unnecessary serious side effects. For these reasons there is an urgent unmet clinical need for a diagnostic assay that identifies the best treatment option for each individual patient.

Previously, SkylineDx developed and validated an in vitro diagnostic medical device – the MMprofiler – which can subtype and reliably predict survival of MM patients on the basis of their own gene signature SKY92. This commercially available test can help in the patient management setting by distinguishing high-risk from standard-risk disease. However, the ability to predict the most effective treatment will greatly expand the clinical value, relevance and utility of such a test. In this project we aim to develop a product, which can help physicians in their treatment decision-making and leading to a personalised medicine strategy that optimizes therapy selection to improve outcome and to minimize treatment related side effects.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far:

In the first month of the second periodic report the requested Amendment (701143-9) was validated. This change included the extension of the project duration with 12 months (until the 30th of April 2020) – to obtain more maturate follow-up to enable a more robust analysis of the data – and the incorporation of a Next-Generation Sequencing (NGS) pilot study. This supplemented in-depth NGS analysis, of a subgroup of the already included patients, will result in additional information that can be used to extend our study for outcome prediction markers and perfectly align with the defined project aims.

The major goal of this period was to recruit additional patient samples and to finalize the gene expression profiling of all material. These objectives were both reached by the simultaneously analysis of the samples in the laboratory and the inclusion of new patient material. By validating the previously established positive contacts, we were able to extend our cohort with samples from the National University Hospital of Singapore, Singapore and the Münchner Leukämielabor, Germany. By combining patients of these clinical institutions, the previous included material and the inclusion of additional trial samples via the Erasmus MC and external UNITO cases, a total study population of 838 MM patient was reached.

Furthermore, the data analysis was started and resulted at present in the successful submission and presentation of multiple abstracts to renowned international conferences, showing treatment specific recommendations for MM patient subgroups.

Moreover, the fourth project team meeting was organized in Stockholm, Sweden on the 14th of June 2018. We had an interactive session in which we discussed the project progress and short term future goals. The meeting was finalized by video interviews in which the different consortium team members provided insights into the current developments of the project for external parties. Other communication efforts were conducted by means of frequently social media posts and project website updates. Furthermore, the MPE and the EUR led a pan-European MM patient questionnaire to assess the current quality of life and collected information about what kind of diagnostic tool is of most value for patients and their doctors when choosing their future treatment.

In the coming months we hope to implement the prepared NGS pilot study efforts, extend our analysis to develop a personalised medicine tool, publish our first scientific papers and continue to work on the regulatory affairs.

Progress beyond the state of the art, expected results until the end of the project and potential impacts (including the socio-economic impact and the wider societal implications of the project so far):

To achieve the consortium’s ambition, genome-wide expression chips and next generation sequencing are employed and analysed by algorithms to extract a unique panel of biomarkers to guide physicians in treatment decision-making. However, for the success of such product it is not only important to outperform the current standard of care – as measured by improvement of quality of life and overall survival, but it is also important that the test has been fully standardized and regulatory approved. For this reason it is a great advantage that the consortium can build on the previously CE-marked MMprofiler. Moreover, for the widespread adoption it is also crucial that the product obtains adequately reimbursement by the healthcare system. To do so, it would be important to show that the introduction will reduce healthcare costs by enabling precision therapy of MM patients and decreasing unnecessary side effects. To assess the complex interplay between social and economic impacts the EUR will perform a detailed medical technology assessment concentrated on our defined focus countries; The Netherlands, United Kingdom, Germany and Italy, which could help establish acceptance in this field.

In addition to its own success, this initiative could become the first showcase that will stimulate the development of new diagnostic tests aiming to enable personalized medicine in other disease areas. In the end, we aim to deliver a state-of-the-art predictive test with a large impact on patients, physicians and healthcare payers.

© MMH2020