SWG Educational Activities
The EICML meeting, initially planned in Windsor, UK in May 2020, was a victim of the COVID-19 pandemic. The workshop style of this meeting together with the opportunities for young and not-so-young investigators to meet and collaborate is less suited to a virtual event but investigators will meet at the same venue in May 2022.
2. ELN Meeting March 2020
This meeting was cancelled consequent in the outbreak of COVID-19
3. ELN Virtual Meeting September 2020
WP4 - CML
CML and COVID-19: Mutual impact of the two diseases. D. Rea (Paris, France)
Results of discontinuation studies in Russia: data of the retrospective and prospective trials. E. Chelisheva (Russian Federation)
Impact of socio-demographics on disease phase and risk, drug choice and treatment outcomes in adults with newly diagnosed CML. Qian Jiang,( Beijing, PR China)
European registry on CML patients in blast crisis. A.-M. Brioli, Jena, Germany, M. Lauseker, (Munich, Germany_
Molecular clones in CML patients affected by the Chernobyl disaster. T. Ernst, Jena, Germany, I. Dyagil, (Kiev, Ukraine)
The new ELN recommendations for treating CML. A. Hochhaus, (Jena, Germany)
CML and HARMONY PLUS Ideas and opportunities. J.M. Hernandez, (Salamanca, Spain); A. Hochhaus, (Jena, Germany); J. Geissler, (Munich, Germany_
WP12/13 - MRD/NGS
Transcript type and DNA PCR in CML. Katerina Machova Polakova (Prague, Czech Republic)
4. ELN Virtual Meeting March 2021
WP4 – CML
New data from the Swedish CML registry Torsten Dahlen (Stockholm, Sweden)
HARMONY PLUS: Introduction Andreas Hochhaus (Jena, Germany)
HARMONY PLUS: Clonal hierarchy in CML Thomas Ernst (Jena, Germany)
CML and COVID-19: Mutual impact of the two diseases. Delphine Rea (Paris, France)
Long-term outcome of imatinib 400 mg compared to imatinib 600 mg or imatinib 400 mg daily in combination with cytarabine or pegylated interferon alpha 2a for CML: results from the French SPIRIT phase III trial. Francois Guilhot (Poitiers, France)
Interim results of a study of de-escalation TKI doses in CML patients. Study of the plasma concentration of TKI in CML patients on therapy with various doses of TKI. Margarita Gurianova (Moscow, Russia)
The ESH-iCMLf John Goldman meeting took place virtually in October 2020. The John Goldman memorial lecture was delivered by Jane Apperley, the Janet Rowley lecture by Ravi Bhatia and the iCML prize was awarded to Dr Sabira Kurtovic. Delegates gathered fron across the world to join the scientific sessions. Special mention shouldl go to the tribute paid at this meeting to Didi Jasmin, who helped develop this particular CML meeting into the international highlight of the CML year and who will sadly be leaving ESH in 2021.
The fifth “EUTOS for CML” project was initiated to ensure the reliable baseline, treatment and outcome data for the collaboration between academia and industry necessary for moving forward on the path to cure. In particular, the treatment option to discontinue tyrosine kinase inhibitors (TKI) demands the highest levels of performance and reliability of quality controlled molecular monitoring.
Since the project kicked off in June 2018, EUTOS has fulfilled its key objectives: the implementation of molecular quality and standardization assessment and the performance of mutational analyses for over 50 reference laboratories across Europe. Based on the individual performance in a well established annual ring trial using the Novartis LYO panel (later Acrometrix® LYO panel), the EUTOS consortium certified 48 European laboratories for deriving lab-specific conversion factors (CFs) as well as their MR4.5 detection ability. Further, the consortium tackled the issue of lab-specific variation of assay performance over time by providing manufactured high/low standards to the reference laboratories and by analyzing 43 data sets.
The EUTOS program was not only designed to ensure highest quality standards for BCR-ABL1 diagnostics. Another of the main drivers of the project was to improve diagnostics by implementing new molecular methods and technologies, integrating the latest scientific developments. A manufactured and calibrated e13a2 BCR-ABL1 reference plasmid showed different amplification dynamics in comparison to the existing e14a2 (ERM- 263) plasmid. While an increasing number of patients are able to discontinue TKI treatment, the biological causes for the loss of treatment free remission (TFR) are still unknown. The EUTOS researchers addressed this question by developing a stratification model to investigate typical and atypical transcripts.
Another approach focused on BCR-ABL1-independent mutations. This study showed no observable, significant difference in the probability of successful treatment discontinuation in patients with ASXL1 mutations and/or other mutations compared to patients with no additional mutations at diagnosis.
The EUTOS group also investigated mutation characteristics in patient cohorts with stable or unstable MMR and generated a mutation profile of patients treated with asciminib. Since studies suggested that CD34+/CD38─ /Lin─stem cells in bone marrow expressing CD26+ may be a new robust biomarker for the identification of CML stem cells, the EUTOS consortium did not recommend the measurement of CD26+ LSC in peripheral blood, as it was suboptimal for the detection of extremely low levels of CD26+ LSC.
A further objective of the EUTOS consortium was to gain a deeper understanding of the maintenance of molecular response of CML patients in TFR driven by immune mechanisms. Among several other findings, T-cell receptor clonality decreases after dasatinib discontinuation. Furthermore, the EUTOS group found that there are changes in the immune cell phenotypes after TKI withdrawal in patients who do not relapse, have fast relapse, or slow relapse. A promising approach for future research would be the identification of a r obust biomarker and/or differential protein patterns regarding the plasma proteome/inflammasome HLA-DR on classical monocytes in CML patients. HLADR significantly correlated with BCR-ABLIS levels after therapy and predicted the achievement of molecular endpoints.
Based on the hypothesis that PD1 might be involved in the regulation of the EUTOS group analyzed 286 patients of the CML-V (TIGER) study. The consortium’s results suggest that targeting the PD1-checkpoint may not be a successful strategy to improve the rate of successful TFR.