CML-3: A comparison study of "toxicity over time" and QoL among all available TKI options

Challenge

Chronic myeloid leukemia (CML) is characterized by the presence of a constitutively active chimeric Bcr-Abl kinase, a product of the BCR-ABL1 chimeric gene. Clinical outcomes have been greatly improved with the use of tyrosine kinase inhibitors (TKIs) targeting Bcr-Abl kinase, and also associated with periodic and chronic adverse events (AEs) that can substantially impact patients’ quality of life (QoL), adherence to therapy and treatment success. Although TKI therapies have been widely used for more than two decades, there is currently little knowledge on time points, transience and cumulative effects of all available TKIs as the periodic and long-time toxicity of available therapies and their impact on patient QoL have only been assessed superficially. Due to this unmet need, this study proposes to obtain toxicity and QoL data from CML patients treated with TKIs and take into consideration all stages of the disease and variable therapy doses, irrespective of the treatment outcome.

Project Partnership

Project Leadership

Tamás Bereczky, LeukaNet, Germany
Torsten Dahlén, Karolinska Institutet
Fabio Efficace, GIMEMA, Italy
Carmen Fava, University of Turin, Italy
Jan Geissler, LeukaNet, Germany
Eglys Gonzalez, LeukaNet/CMLAN, Germany
Edoardo La Sala, GIMEMA, Italy
Gastone Castellani, University of Bologna, Italy

Impact

To better understand time points, frequency, transience and cumulation of AEs related to disease characteristics and CML.
To influence patient management by clinicians, caregivers and even patients themselves to potentially improve the QoL of CML patients.
To establish a relationship between toxicity and impact of quality of life
To impact patient empowerment by increasing the knowledge on long-term TKIs toxicity and QoL affection by the different therapies

Project Summary

This research aims to describe short-term and long-term toxicity (incidence, transience and cumulation) identified in all CML patients treated with TKIs and its correlation with QoL, regardless of the treatment outcome. This retrospective, non-interventional study will obtain toxicity and QoL data from CML patients treated with TKIs which will consider all disease stages and variable therapy doses. Data will be sourced from academic and commercial CML clinical studies where Common Terminology Criteria for Adverse Events (CTCAE) and patient-reported outcome (PRO) data are available. The data will be analyzed and reported in a descriptive manner. Factors such as side effects and symptoms will be described by frequency or presence/absence and factors such as timepoints will be reported in a quantitative manner.

Access to a larger dataset of CML patients through the HARMONY Alliance Big Data Platform will offer a better insight into when and how often these side effects occur, resolve and accumulate. By understanding the periodic, short-term and long-term toxicity and side effect burden, this research can help to determine the optimum order in which patients are prescribed drugs and optimize the outcome of TKI treatment.

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).