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 DSC3463 KopieAlliance 2: The iCMLf TFR Alliance

Maximising achievement of TFR while minimising failed TFR attempts and other negative outcomes

The iCMLf has recently launched a second Alliance under the banner of CURE - the iCMLf Treatment-Free-Remission (TFR) Alliance. The mission of the iCMLf TFR Alliance is to maximise achievement of TFR while minimising failed TFR attempts and other negative outcomes.


The dramatic success of tyrosine kinase inhibitors (TKIs) has led to the widespread perception that chronic myeloid leukemia (CML) has become another chronic disease, where lifelong commitment to pharmacological control is the paradigm. Recent scientific findings demonstrate that some CML patients who have achieved stable deep molecular response can safely stop their therapy without relapsing. Furthermore, those who are unsuccessful in their cessation attempt can safely re-establish remission after restarting their TKI therapy. Hence, the concept of treatment-free remission (TFR) is currently being discussed intensively in the CML changing our approach for the many CML patients who have achieved a stable deep molecular response on long-term TKI therapy. Perhaps half of these patients could successfully achieve TFR if offered the opportunity.

For many of these patients ongoing therapy is impairing quality of life and imposing a heavy financial burden while arguably achieving nothing. This recommendation is based on the evident safety of cessation attempts and TFR in the clinical trial setting. We acknowledge that there are potential risks associated with cessation attempts in wider clinical practice, but this should not deter us. Instead we need to establish criteria for safe and appropriate TKI cessation. Clinical trials will enable us to define the best strategies to achieve TFR, but clinicians need guidance today about how to approach this issue with their patients. We outline circumstances in which it would be in the patient's best interest to continue TKI, as well as criteria for a safe TFR attempt.

Planned priorities of the TFR Alliance

  • Develop and assess clinical predictors of TFR
  • Develop and assess biomarkers of TFR
  • Clinical registries and trials of TFR
  • Virtual tissue bank of TFR samples
  • Disseminate a correlative study collection and storage protocol for TFR studies
  • Assess safety of current TFR practice
  • Assess long-term outcomes - is TFR safer than long-term TKI therapy for patients in deep molecular response (DMR)

The focus of the current work is on safety of TFR

Project I will investigate the long-term safety of TFR by establishing a global TFR registry.

  1. Determine the incidence of advanced phase CML in patients who have discontinued TKI therapy with the aim of TFR.
    The iCMLf TFR Alliance plans to bring together 10-12 regional or local TFR registries to provide a pool of 2,000 patients who have attempted TFR. This will enable us to make an initial estimate of the rate of AP/BC per year in this risk group. Then we will rapidly accumulate the critical data on all the patients within the Global TFR registry. We expect to be able to retrospectively analyse approx. 6,000 patient-years.

  2. Determine whether the risk of acute phase CML is higher in the TFR setting than the 'background level' in equivalent patients.
    This 'background rate' would be determined by following patients who were eligible for a TFR attempt but have remained on TKI therapy. The iCMLf TFR Alliance plans to collaborate with pharmaceutical companies to extract the data from the large randomised studies where molecular response and long-term disease progression data and survival are available, as well as academic studies.

Project II will work on case studies in blastic transformation and other outcomes.
Key activities are;

  • Investigate the clinical and biological features of patients who progressed to blast crisis following a TFR attempt
  • Identify what samples are available for correlative studies
  • Identify investigator in each country who would be responsible for gathering the critical information on BC cases
  • Investigate the clinical and biological features of any patient who had an adverse outcome following a TFR attempt
  • Gain a best estimate of the number of patients who have attempted TFR from the regions where BC cases were collected

Grants-in-aid for research projects on TFR when considering lifestyle factors

Coming later in 2021. Register your interest at

Current iCMLf TFR Alliance members

  • Timothy Hughes (SAHMRI / University of Adelaide) (Chair)
  • Jane F Apperley (Imperial College, London)
  • Charles Chuah (Cancer and Stem Cell Biology Signature Research Program, Duke-NUS Medical School, Singapore and Department of Haematology, Singapore General Hospital)
  • Richard Clark (University of Liverpool)
  • Simone Claudiani (Imperial College Healthcare NHS Trust, London)
  • Jorge Cortes (MD Anderson Cancer Center, University of Texas)
  • Michael Deininger (Huntsman Cancer Institute, University of Utah, Salt Lake City)
  • Brian J Druker (Division of Hematology and Medical Oncology, Oregon Health & Science University Knight Cancer Institute, Portland and Howard Hughes Medical Institute, Portland)
  • J. Valentin Garcia Gutierrez (Hospital Universitario Ramón Y Cajal)
  • Jan Geissler (CML Advocates Network)
  • Nobuko Hijiya (Columbia University, New York)
  • Carlo Gambacorti-Passerini (University of Milano Bicocca, San Gerardo Hospital, Monza)
  • Andreas Hochhaus (Universitätsklinikum Jena)
  • Dennis Kim (Princess Margaret Cancer Centre, Toronto)
  • Dong-Wook Kim (Yonsei University Hospital Seoul)
  • Francois-Xavier Mahon (University of Bordeaux)
  • Michael J Mauro (Myeloproliferative Neoplasms Program, Leukemic Service, Memorial Sloan Kettering Cancer Center, New York)
  • Dragana Milojkovic (Imperaial College Healthcare NHS Trust, London)
  • Satu Mustjoki (University of Helsinki)
  • Tiong Ong (Duke NUS Medical School)
  • Carolina Pavlovsky (Fundaleu, Buenos Aires)
  • Jerry P Radich (Fred Hutchinson Cancer Center, Seattle)
  • Delphine Réa (Hospital Saint-Louis, Paris)
  • Susanne Saußele (University of Mannheim)
  • Giora Sharf (CML Advocates Network)
  • Naoto Takahashi (Akita University, Akita)