CML-2: Using Big Data to Map and Identify Optimal Treatment Pathways to Treatment-Free Remission in CML

Challenge

Only 10‒30% of patients with chronic myeloid leukemia (CML) achieve treatment-free remission (TFR) because the factors that determine successful discontinuation of tyrosine kinase inhibitors (TKIs), the current cornerstone of CML care, remain poorly understood. Mapping the optimal treatment pathway that gives the greatest chance of a successful TKI discontinuation attempt could help to make TFR a clinical reality for more patients.

Project Partnership

Planned projects partners are: Karolinska Institutet, Swedish CML register (Sweden); South Australian Medical Research Institute (Australia); Bergonie Cancer centre Bordeaux - Bordeaux university - FiLMC french Group (France), Chang Gung Memorial Hospital - Nationwide TFR register(Taiwan), Fundaleu Hospital and Clinical Research Center Buenos Aires (Argentina), Hopital Saint-Louis APHP (France), Hospital Santa Marcelina (Brazil), Hospital Universitario de Gran Canaria Dr. Negrín (Spain), Imperial College London (UK), Instituto do Cancer do Estado de Sao Paulo (ICESP) (Brasil), Faculdade de Medicina da Universidade de Sao Paulo (USP)(Brasil), Italy Instituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori" (Italy), Peking University People's Hospital (China), Princess Margaret Cancer Centre - University of Toronto (Canada), Singapore General Hospital/Duke-NUS Medical School (Singapore), South Australian Health and Medical Research Institute (South Australia), The Czech Leukemia Study Group for Life - nationwide collaboration (Czech Republic), Universitätsmedizin Mannheim der Universität Heidelberg - Deutsche CML Studiengruppe (Germany), Université Versailles Saint Quentin en Yveline - Centre Hospitalier de Versailles - French CML group (FiLMC) (France), Brazil University Hematology Center (Brazil), University of Liverpool (UK), Italy University of Turin - Italian TFR register (Italy).

Project Leadership

Torsten Dahlén, Karolinska Institutet, Stockholm, Sweden
Timothy Hughes, South Australian Medical Research Institute, Adelaide, Australia
Francois-Xavier Mahon, Bergonie Cancer Centre, Bordeaux University and FiLMC French Group, France

Impact

To create a better understanding of the key factors that predict and influence relapse risk after discontinuation of TKIs
To identify the optimal treatment pathway leading to an increased likelihood of achieving successful and prolonged TFR
To refine existing clinical guidelines, and reshape the design of future clinical trials, with the ultimate aim of making TFR a universal expectation for all CML patients

Project Summary

This project will harness the HARMONY Big Data Platform, together with pooled data from multiple international collaborators within the International CML Foundation Treatment-Free Remission Alliance (iCMLf TFR Alliance), to explore the multiple factors that drive outcomes after TKI discontinuation.

The study will include a total cohort of over 2.000 CML patients and will focus on four specific aims:

To study TKI treatment pathways: notably the impact of individual agents, treatment sequencing/combinations, treatment duration and level of clinical response on subsequent relapse risk
To build and evaluate a model to predict the risk of molecular relapse after TKI discontinuation
To explore key patient outcome measures such as quality of life pre- and post-treatment discontinuation (if data availability allows)
To collect and store tissue sample data in a virtual database to facilitate future collaborative research in this field.

As the HARMONY Big Data platform is the largest TFR CML register in Europe, it is hoped that this research will help bridge existing gaps in knowledge and pinpoint the optimal treatment pathway leading to TFR for patients with CML. This would allow for better guided clinical care of CML, helping more patients to successfully discontinue treatment and paving the way towards a possible cure.

Public-private partnership for Big Data in Hematology

HARMONY and HARMONY PLUS are 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. Funding is received from the IMI 2 Joint Undertaking and is listed under grant agreement for HARMONY No. 116026 and grant agreement for HARMONY PLUS No. 945406. 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).