Highlights from the SWG

ELN Management Recommendations for CML:
Ongoing

Meeting activities for promotion of cooperative research in the field of CML

EUTOS (European treatment and outcome study):
2016-2018
2019-2022

Private-public partnership with Novartis:
12 participants in 7 European countries.

The overall objectives of this CML collaboration are:

  • Promote quality controlled molecular monitoring and mutational analyses using standardized RQ-PCR technologies, including definition and validation of an international definition of molecular response, and further expand the validation of laboratory measuring BCR-ABL according to International Scale
  • Establish new methods to evaluate molecular response on the stem cell level
  • Enhance the cooperation among European scientists to provide a platform for the expedited evaluation of new treatments, combination and discontinuation strategies with the objective of progressing towards curing CML.

1. SWG Session at EHA25

ELN-EHA SWG for CML: CML - What is new?

Chair: Rüdiger Hehlmann (DE)

  • What is the minimal duration of DMR and treatment for optimal outcome of relapse-free treatment discontinuation?

Francois-Xavier Mahon (FR)

  • Impact of generics on CML treatment

Jeffrey Lipton (CA)

  • Mechanisms and management of TKI resistance

Philippe Rousselot (FR)

Most relevant advancements in CML:

For more information about relevant advancements in CML during 2020, please refer to pages 51-59 of the Educational Updates in Hematology Book of the 25th Congress of the European Hematology Association here.

2. CML in the EHA Research Roadmap

TKIs have substantially improved the survival of CML patients and there is now a reasonable  expectation that a significant proportion of patients will be cured. The main objective of the EHA SWG is to integrate the leading European national trial groups in CML

to form a cooperative network for advancements in CML related research and health care. Within the group of European Investigators on CML (EICML), a clinical trials platform was

created to promote the performance of clinical trials with new drugs and/or treatment strategies. Standardization of diagnostic and therapeutic procedures allows outcome comparison across Europe. We aim to improve  tolerability of the treatment, the rate of deep molecular responses and  the proportion of patients in durable remission after stopping TKI. Enhanced inhibition of BCR-ABL1 with more specific inhibitors or drug combinations are possible strategies to improve TFR by increasing the rates of deep molecular response. Clinical approaches utilizing immune surveillance to eradicate residual leukemic cells are potential future research directions to improve TFR rates. Despite major

improvements in the standard of care for CML, the complexity of CML blast crisis pathophysiology, together with the failure of TKIs to eradicate CML at the stem cell level, as well as the observation of molecularly defined BCR-ABL1 negative clones demand further research. A better understanding of the events governing leukemic stem cell behaviour might lead to the biological cure of CML and effective treatment of blast crisis.

Biostatisticians and patient advocacy groups cooperate with the study groups with a European clinical trials platform which will support the coordination of the studies.

3. CML joins HARMONY

HARMONY was initiated in January 2017 for a period of five years, and is funded through the European Union's (EU's) Innovative Medicines Initiative (IMI). Capitalizing on its strong drive to succeed, on a spirit of international cooperation, and on the availability of high-speed technologies, HARMONY will facilitate better access to therapy, improved patient care, and a higher quality of life, all accomplished in compliance with legal, ethical, and governance rules. Its results will revolutionise the treatment of hematologic malignancies (HMs).

In June 2021 we launched a new project in HARMONY focussed on CML. There is a need for a global platform to systematically evaluate the mutational landscape of CML at diagnosis, during treatment, should resistance occur, and in advanced disease. This will provide evidence for informed expert international clinical practice guidelines for genomic-based monitoring in CML. As the HARMONY BigData platform will be the largest CML register in Europe this analysis would greatly bridge the gap in knowledge and could significantly contribute to improved outcome for patients with CML.

Under the leadership of Thomas Ernst and Susan Branford, we will harness the wealth of genomic information that is generated in local CML research projects by building a platform to facilitate data assimilation and analysis in order to evaluate the clinical relevance of these variants. We aim to discover biomarkers that could predict treatment response and progression, and guide drug use and development. Participating laboratories will contribute data to answer key clinical questions related to;

  • BCR-ABL1 independent mutations at diagnosis
  • The evolution of BCR-ABL1-independent clones during TKI therapy
  • Molecular aberrations during advanced phase disease
  • Mutations detected in single cells and specific cell populations, which might point towards strategies to increase the number of patients who achieve treatment-free remission

To read more go to https://www.harmony-alliance.eu/projects/research-project/cml-understanding-the-clonal-hierarchy-in-chronic-myeloid-leukemia-to-help-improve-patient-outcomes

4. Joerg Hasford 1950-2021

It is with deep regret that we announce the death of Joerg Hasford in June 2021. In 1984, Joerg joined the South German Hemoblastosis Group study on chronic myeloid leukemia, to supervise the statistical analysis of the first controlled CML study in Germany. At the time it was considered the most boring study in Germany but Joerg stayed with CML and was integral to the design and analyses of the well-executed series of German studies that saw CML move from an incurable disease to one compatible with a normal life-span. He is especially remembered for the Hasford score, an algorithm to predict prognosis based on simple diagnostic parameters, for which he received the Paul Martin Prize in 2000. In addition to being a founder member of the European Investigators in CML (EICML) in 1993, he was active from the earliest years of the German Competence Network for Acute and Chronic Leukemia and the European LeukemiaNet, taking particular responsibility for the European CML Registry of the EUTOS cooperation between European LeukemiaNet and Novartis.