The HARMONY Alliance is a large public-private European Network of Excellence for Big Data in Hematology, established in January 2017 and funded by the Innovative Medicines Initiative (IMI).
Although the cytogenetic heterogeneity of AML has been recognized for many decades, the molecular heterogeneity of the disease has been identified only over the past 15 years. The prognostic value of the heterogeneity is widely accepted. However, translation of this molecular information into improved therapeutic regimes is slow. In its first pilot project, HARMONY is combining patient information from the German Austrian AML Study Group (AMLSG) and the HOVON – the Haemato Oncology Foundation for Adults in the Netherlands- registries with the aim to further improve disease classification and better understand the genomic context, to identify other prognostic factors and to monitor outcomes with current treatment and new therapies in different subtypes of adult AML. In this context, Novartis has provided anonymized data from the RATIFY trial.
“HARMONY will become an invaluable tool to better understand the heterogeneity of hematologic malignancies and to move big data analysis to the next level”, says Hartmut Döhner from HARMONY Partner, Ulm University Hospital and chair of the German-Austrian AML Study Group (AMLSG). Ulm University Hospital provided 1540 datasets.
Novartis shared data from the Rydapt (midostaurin) RATIFY study, the largest clinical trial in FLT3-mutated AML to date, performed to determine the effect of adding midostaurin, a multitargeted kinase inhibitor, to standard chemotherapy in patients with AML and a FLT3 mutation. This data, which was anonymized before transfer, will be integrated and analyzed along with data from a number of other high-quality sources within HARMONY, to help better define clinical endpoints and outcomes for AML.
The Phase III RATIFY trial was run in collaboration with the Alliance for Clinical Trials in Oncology (CALGB). It included 717 study participants from around the world. The full results, which showed significant overall survival benefit for FLT3+ AML patients consistently across FLT3 mutation subgroups, were published in the New England Journal of Medicine in June 2017 under the senior authorship of the HARMONY Key Opinion Leader Hartmut Döhner (ref Stone RM et al. N Engl J Med. 2017 Aug 3;377(5):454-464). Based on data from RATIFY, The National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology for AML now include the use of midostaurin in FLT3-mutated AML.
“With such positive efforts in sharing aggregated data of hundreds of patients into the HARMONY platform, the hope is that other data custodians across industry and academia will also be inspired to join the HARMONY Alliance. In the future, the aspiration is that the HARMONY Alliance model will allow us to create a blueprint that can be applied to future projects in other disease areas, ultimately benefiting many more patients in Europe and well beyond”, states Mirko Vukcevic from Novartis, HARMONY Project Lead.
Other datasets (680) come from the Erasmus University Medical Center in Rotterdam. The department of Hematology has been engaged in the collection of genomics data sets of clinically well-annotated patients enrolled in the international multicenter HOVON-SAKK AML trials. This way they will contribute the published data sets – which include gene expression data (Affy), copy number data (Affy), and targeted NGS data of AML – to HARMONY.
“This data will give better insight into the heterogeneous disease AML,” says Dr. Peter Valk from Erasmus MC, HARMONY Partner, who focuses in his research on the molecular analyses of various hematologic malignancies, mainly acute myeloid and lymphoblastic leukemias.
In the next generation sequencing era, large data sets of (subset of) acute myeloid and lymphoid leukemias of patients enrolled in the HOVON-SAKK clinical trials will be generated. These data sets currently comprise targeted gene panels on AML cases at diagnosis and after high dose induction treatment but will also include whole exome and whole genome data in the future. They will also be contributed to the HARMONY Alliance.
The first three data sources are just the beginning. More HARMONY Partners and Associated Members are getting ready to upload their anonymized data from clinical trials or other research projects to the HARMONY Big Data Platform. Furthermore, it is not a one-off process with a specified end. Big Data analysis will be carried out over a long period of time. Alongside the gradually added and upgraded data sets and rising amounts of information, a data mining process will enable us to make new discoveries in the connected databases.
About the HARMONY Alliance: a public-private European Network of Excellence for Big Data in Hematology, established in January 2017. Our mission is to unlock and spread valuable knowledge on hematologic malignancies (blood cancers) among a large number of stakeholders, with the goal to harness and mine Big Data to speed up the development of improved treatments for patients and more effective treatment strategies.
HARMONY currently has 53 Partners and 32 Associated Members from 22 countries. HARMONY is funded through the Innovative Medicines Initiative (IMI), Europe's largest public-private initiative aiming to speed up the development of better and safer medicines for patients.
HARMONY has received funding from IMI 2 Joint Undertaking and is listed under grant agreement No. 116026. This Joint Undertaking receives support from the European Union’s Horizon 2020 Research and Innovation Programme and the European Federation of Pharmaceutical Industries and Associations (EFPIA). IMI supports collaborative research projects and builds networks of industrial and academic experts in order to boost pharmaceutical innovation in Europe.
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