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Validation of a personalised medicine tool for Multiple Myeloma that predicts treatment effectiveness in patients

Periodic Reporting for period 3 - MMpredict (Validation of a personalised medicine tool for Multiple Myeloma that predicts treatment effectiveness in patients)

Reporting period: 2019-04-01 to 2020-10-31

The Horizon 2020 MMpredict initiative was started on November 1st 2016 and included the following consortium partners: SkylineDx, the Department of Haematology of the Erasmus University Medical Centre Rotterdam, the Department of Onco-Haematology of the University of Turin, the Institute for Medical Technology Assessment of the Erasmus University Rotterdam (EUR) and the Myeloma Patients Europe (MPE), combining a small to medium-sized enterprise specialised in molecular diagnostics, two clinical centres with 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 (PCs), which are specialized white blood cells located within the interior of larger bones. Here, embedded in the 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 PCs 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. 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, 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 MMprofilerTM - 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.
In the first month of the final project period the consortium has completed the patient database. It consisted of 838 MM patient with full microarray-based data and a subgroup of 272 individuals with additional Next Generation Sequencing (NGS) information available. This is a very valuable dataset because it consists of a large group of patients with high quality clinical annotation, genetic information, treatment data and associated survival metrics. Combining all this information empowered the bioinformatics discovery of predictive biomarkers which resulted in two peer-reviewed publications and multiple successful presentations at renowned conferences, showing treatment specific recommendations for MM patient subgroups.

On the 12th of June 2019 we organized the fifth project team meeting in Amsterdam, The Netherlands and additionally virtual meetings were conducted. In these interactive sessions we discussed the project progress which is illustrative for the good communication amongst the consortium members and we anticipate that the end of the MMpredict project will not be the end for our collaborations.

Furthermore, the consortium has requested a second Amendment request (AMD-701143-20). Due to the present COVID-19 situation, we were unable to adequately finalize the last project deliverables. Within this amendment we accommodated all pending tasks and actions with an extended project duration of 6 months. Due to the effective implementation of the validated Amendment request, we succeeded to complete the MMpredict project. This included the preparation of the final periodic report and a long list of deliverable reports such as the Treatment decision matrix, the Analytical validation report, the Medical technology assessment, the Regulatory affairs report. Moreover, all stakeholders were updated by means of frequently social media posts, dedicated sessions and project website updates. In addition, webinars were organized by the MPE to educate MM patients about precision medicine and its future perspectives including the MMpredict project and the EUR led the data analysis and writing of a paper about the previously conducted pan-European quality of life (QoL) assessment under MM patient.

In conclusion, we have been able to discover and report about biomarkers that can select specific MM patient subgroups that have a particular benefit of some defined clinical treatment strategies. In the coming months we hope to further reinforce the development of our personalized medicine tool by publishing our findings in additional scientific papers and presentations at congresses. Moreover, the described results will be implemented within the updated regulatory framework and we hope to file the analytically validated MMpredictor test.
To achieve the consortium’s ambition, micro-array chips and NGS 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 QoL and survival, but it is also important that the test has been 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 adequate 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 performed an initial medical technology assessment on one of the first findings concentrated on our defined focus countries. The proposed first biomarker-stratified approach resulted in higher costs for a substantial gain in survival and QALYs.

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.
Group picture from the project team meeting in Amsterdam, June 12th 2019
Group picture from the project team meeting in Rotterdam, December 15th 2017
Introduction image of the project video recorded by the Myeloma Patients Europe (MPE)