The Multiple Myeloma horizon 2020 (MMh2020) 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, 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

The project started with a kick-off meeting in October 2016, during which patient sample recruitment and laboratory work-up were agreed upon. For the analysis of the data, we decided that it would be preferable to focus on drug classes as well as individual drugs. Furthermore, the set-up of the health economic model for the medical technology assessment by the EUR was discussed and the MPE offered to use their established network to get in contact with MM patients via different associated European patients.

The first months of the project were mainly devoted to the inclusion and recruitment of MM patient samples from internal biobanks. To accommodate samples in the study a database was developed, after which the first patient material was included, shipped and analysed. Simultaneously, the project website was constructed and several medical experts treating MM were contacted for an interview about the current treatment guidelines, which – in combination with an intensive study of the European treatment guidelines – resulted in a report about the current treatment regimens. Moreover, for the inclusion of samples from the UNITO, an informed consent was written and approved by the local medical ethical committee after which Italian patients were also included in the study.

In the subsequent period multiple European clinical institutions were contacted for the recruitment of additional patient samples of which some still investigate the availability of eligible samples. However – for various reasons – the recruitment did not completely proceed as anticipated. During the second project team meeting in June 2017, this subject was addressed and additional efforts will be invested to recruit extra samples from external sites.

At the third project team meeting in December 2017, the consortium partners and EC project officer were informed about the investigated costs per treatment for MM medication and the currently included 506 samples, of which 306 completed the gene expression profiling. Furthermore, the preliminary study results and an amendment request – the extension of the project duration and addition of a pilot study – were discussed.

In the coming months we hope to complete the database, aiming to include the 800 bio-banked patient samples for which we have positive leads established. Moreover, we will work on processing all patient samples in the lab, start disseminating the developed quality of life patient questionnaire, 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 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