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Chronic Myeloid Leukemia

Treatment free remission (TFR) -  CML -  Chronic Myeloid Leukemia


Treatment free remission in CML refers of maintenance of deep molecular response without continuing TKI therapy after achieving undetectable molecular residual disease (UMRD)
Treatment free remission in CML refers of maintenance of deep molecular response without continuing TKI therapy after achieving undetectable molecular residual disease (UMRD)
​
Important notice: You must  inform your CML doctor or a qualified doctor if you want to stop your medication. The material presented here is for information  purposes only; it is not a substitute for your physician’s guidance and care....   See our disclamer             
                 
"Treatment-free remission (TFR) has recently emerged as a goal of treatment in chronic myeloid leukaemia (CML). Molecular remission is sustained in around 30% of imatinib-treated patients who stop treatment after ≥2 years with undetectable minimal residual disease (UMRD) by conventional real-time reverse transcription polymerase chain reaction. An additional 20–30% of patients will lose UMRD, but remain in stable major molecular remission off treatment. Most patients with molecular recurrence have a significant increase in BCR-ABL1 within the first 6 months off treatment, but there are also rare late relapses. As re-treatment with imatinib restores control, a trial of TFR is safe so long as careful molecular monitoring is provided to enable prompt re-treatment. The minimum eligibility criteria for a trial of TFR are not yet defined, but the available data support a MRD level of around a molecular response of 4·5 log for at least 2 years. Factors associated with a higher probability of TFR include low risk Sokal score, prior interferon treatment, longer total duration of imatinib treatment and higher numbers of natural killer cells at the time of imatinib discontinuation. Preliminary data suggest that the rate of TFR in patients treated with more potent tyrosine kinase inhibitors will probably be higher. The biology that underlies TFR is an area of active investigation."

Extract of " How I determine if and when to recommend stopping tyrosine kinase inhibitor treatment for chronic myeloid leukaemia "
VIDEOS

Treatment-free remission in chronic myeloid leukaemia
November 2, 2017, cmladvocates

World CML Day: Treatment-free remission
September 22, 2017,  Leukaemia Care

What is the best treatment in the next few years to achieve more treatment-free remission in CML?
July 25, 2016, VJHemOnc

CML Stop Treatment: Dr David Ross | Rising Sun Meeting 2015
February 17, 2016, The Max Foundation

Michael Mauro Discusses Therapy-Free CML Remission
Decmber 31, 2015, OncLiveTV

The patient perspective on treatment-free remission, including support needs - Pat Elliot 
May 2015, CML Horizons Barcelona

Treatment-free remission, stop trials, predictors for stopping treatment  - Andreas Hochhaus
May 2015, CML Horizons Barcelona  

Panel discussion: The psychology of stopping treatment
May 2015, CML Horizons Barcelona  

Treatment free remission: opportunities and dangers - Alok Srivastava
March 16, 2015, iCMLf

Discontinuation of Treatment With TKIs in Chronic Myelogenous Leukemia   
January 10, 2014, OncLive

Is Stopping CML Treatment a Viable Option Now?                                                       
January 17, 2013,
Patient  Power

Can we safely stop TKI therapies? Experience from the STOP trials - Dr. Delphine Rea
December 2012, iCMLf

Could Some Patients Stop Taking Their CML  Pills?                                 
October 2010, Patient Power


TRIALS

European Stop Tyrosine Kinase Inhibitor Study (EURO-SKI)

Treatment-free Remission Accomplished With Dasatinib in Patients With CML (TRAD)

Treatment-free Remission After Achieving Sustained MR4.5 on Nilotinib (ENESTop)

Nilotinib Treatment-free Remission Study in CML (Chronic Myeloid Leukemia) Patients (ENESTFreedom)

De- Escalation and Stopping Treatment of Imatinib, Nilotinib or sprYcel in Chronic Myeloid Leukaemia (DESTINY)

Randomized Phase III Study to Assess the Effect of Longer Duration of Consolidation Treatment With Nilotinib on TFR in CP CML

FORUMS

Those in remission continue doing well on TKI long-term   by Asian  CML Support Group
TFR Series 1-What is TFR
TFR Series 2-Risks of stopping and continuing drugs
TFR Series 3-Who Should NOT go off drugs
TFR Series 4-Monitoring in TFR by Asian CML Support Group
TFR Series 5-Case Studies (Important from Dr. Hughes article)  by Asian CML Support Group
TFR Series 6- Pros and Cons of Treatment Discontinuation by Asian CML Support Group


                                                          FACEBOOK

CML Patients in TFR (Treatment Free Remission)  +++ private group on Facebook
U.S. TFR/LAST Trial Participants   +++ public group on Facebook
​

ARTICLES

Anxiety and depression associated with tyrosine kinase inhibitor discontinuation in patients with chronic myeloid leukemia
April 12, 2018, PubMed

When to Stop Tyrosine Kinase Inhibitors for the Treatment of Chronic Myeloid Leukemia
March 8, 2018, Current Treatment Options in Oncology

Second-line Nilotinib May Lead to Treatment-Free Remission in Chronic Phase CML
March 5, 2018,  Oncology Nurse Advisor

Treatment-Free Remission Assessed After Nilotinib Discontinuation in CML
February 26, 2018, Monthly Prescribing Reference

Defining therapy goals for major molecular remission in chronic myeloid leukemia: results of the randomized CML Study IV
February 26, 2018, Nature

Durable treatment-free remission in patients with chronic myeloid leukemia in chronic phase following frontline nilotinib: 96-week update of the ENESTfreedom study
February 22, 2018, PubMed

​Considerations for Successful Treatment-free Remission in Chronic Myeloid Leukemia
February 2018,  Clinical Lymphoma, Myeloma & Leukemia


Treatment-free remission in CML: who, how, and why?
December 8, 2017, PubMed

An e13a2 Type of BCR-ABL Transcript  Has a Significant Adverse Impact on the Achievement of a Sustained Deep Molecular Response and on the Maintenance of a Treatment Free Remission after Stopping Tyrosine Kinase Inhibitors
December 2017, ASH 2017

Pilot Study of Imatinib Discontinuation in Patients with Chronic Myeloid Leukemia with Deep Molecular Response (EDI-PIO) – Evaluation of Pioglitazone in Treatment-Free Remission
December 2017, ASH 2017
 
Long-Term Follow-up of the ALLG CML8 Twister Study of Treatment-Free Remission (TFR) in Patients with Chronic Myeloid Leukemia (CML)
December 2017, ASH 2017
 
Impact of Treatment Cessation on Overall Disease Outcomes in Patients with Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Attempting Treatment-Free Remission (TFR): Findings from Enestfreedom and Enestop
December 2017, ASH 2017
 
Treatment-Free Remission (TFR) Among Patients (pts) with Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Not Initially Eligible for Treatment Discontinuation Due to Unstable Deep Molecular Response (DMR): Enestfreedom and Enestop
December 2017, ASH 2017

Interim Results of the Canadian Tyrosine Kinase Inhibitor
Discontinuation Trial for 2nd Attempt of Treatment Free Remission: Treatment Free Remission Accomplished By Dasatinib (TRAD)

December 2017, ASH 2017

Treatment-free remission in patients with chronic myeloid leukemia
July 8, 2017, Pubmed

Immune Effector Recovery in Chronic Myeloid Leukemia and Treatment-Free Remission
April 24, 2017, NCBI

Low body weight and body mass index may be associated with musculoskeletal pain following imatinib discontinuation in chronic myeloid leukemia
April 12, 2017, PublMed

CD86+ pDCs: A Marker for Treatment-free Remission in Chronic Myeloid Leukemia?
March 1, 2017, Cancer Therapy Advisor

CML: Less Frequent Monitoring of BCR-ABL1 May Not Affect Outcomes
February 28, 2017, Cancer Therapy Advisor

New CML Data Post Signs on Route to Treatment-Free Remission
February 10, 2017, Medscape

Immune reconstitution and remission in CML
2017, Blood

Treatment-Free Remission in Patients with Chronic Myeloid Leukemia in Chronic Phase According to Reasons for Switching from Imatinib to Nilotinib: Subgroup Analysis from ENESTop
December 5, 2016,  ASH 2016
 
Patient-Reported Quality of Life before and after Stopping Treatment in the ENESTfreedom Trial of Treatment-Free Remission for Patients with Chronic Myeloid Leukemia in Chronic Phase
December 4, 2016,  ASH 2016

Two-Year Consolidation By Nilotinib Is Associated with Successful Treatment Free Remission in Chronic Myeloid Leukemia with MR4.5:  Subgroup Analysis from STAT2 Trial in Japan
December 3, 2016,  ASH 2016
 
Patient-Reported Quality of Life before and after Stopping Treatment in the ENESTop Trial of Treatment-Free Remission for Patients with Chronic Myeloid Leukemia in Chronic Phase
December 3, 2016,  ASH 2016
  
Characterisation of Molecular Relapse Profiles after Tyrosine Kinase Inhibitor Cessation in Patients Eligible for Treatment-Free Remission Strategies in Chronic Phase CML
December 3, 2016,  ASH 2016
 
Treatment-Free Remission Accomplished By Dasatinib (TRAD): Preliminary Results of the Pan-Canadian Tyrosine Kinase Inhibitor Discontinuation Trial
December 3, 2016,  ASH 2016
 
Treatment-Free Remission (TFR) in Patients with Chronic Phase Chronic Myeloid Leukemia (CML-CP) and in Stable Deep Molecular Response (DMR) to Dasatinib – the Dasfree Study
December 3, 2016,  ASH 2016

CML patient motivation for TFR remission attempts highlighted
October 28, 2016, medwireNews

Rationale and motivating factors for treatment-free remission in chronic myeloid leukemia
August 10, 2016, Leukemia & Lymphoma

Telomere length shortening is associated with treatment-free remission in chronic myeloid leukemia patients
July 29, 2016,  Journal of Hematology & Oncology

The concept of treatment-free remission in chronic myeloid leukemia
June 3, 2016, Leukemia

Treatment-free remission (TFR) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) treated with second-line nilotinib (NIL): First results from the ENESTop study (1)
June 2016, ASCO 2016

Treatment-free remission (TFR) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) treated with second-line nilotinib (NIL): First results from the ENESTop study  (2)
June 2016, ASCO 2016

Moving treatment-free remission into mainstream clinical practice in CML
March 22, 2016, Journal Blood

Effect of Nilotinib Treatment Duration on Treatment-Free Remission in Patients with CP-CML
February 2016,  The Oncology Pharamacist

How I Told My Kids I Quit the Medication That Saved My Life
January 4, 2016,  Yahoo Parenting

Treatment-Free Remission (TFR) Eligibility in Patients (pts) with Chronic Myeloid Leukemia in Chronic Phase (CML-CP) and Residual Disease on Long-Term Imatinib (IM) Who Switched to Second-Line Nilotinib (NIL)
December 7, 2015, ASH 2015

Enestpath: A Phase III Study to Assess the Effect of Nilotinib Treatment Duration on Treatment-Free Remission (TFR) in Chronic Phase-Chronic Myeloid Leukemia (CP-CML) Patients (pts) Previously Treated with Imatinib: Interim Analysis from the First Year of Induction Phase
December 7, 2015, ASH 2015

When to Stop Beneficial Treatment in Chronic Myeloid Leukemia
November 25, 2015, Curetoday.com

Dasatinib Discontinuation After 1 Year Feasible in Certain Patients With CML
November 10, 2015, Cancer Therapy Advisor

Conditional survival in patients with chronic myeloid leukemia in chronic phase in the era of tyrosine kinase inhibitors
October 19, 2015, PublMed

ASH-Report #1: Stopping CML treatment for therapy-free remission
January 25, 2015,  CML Advocates Network

Attitudes and Perceptions of Patients (pts) with Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Toward Treatment-Free Remission (TFR)
September 6, 2014, Journal Blood

Musculoskeletal Pain in Patients With Chronic Myeloid Leukemia After Discontinuation of Imatinib: A Tyrosine Kinase Inhibitor Withdrawal Syndrome
2014, American Society of Clinical Oncology

Musculoskeletal Pain May Be Sign of Potential Tyrosine Kinase Inhibitor Withdrawal Syndrome in CML
August 1, 2014, The ASCO Post

Musculoskeletal Pain on Stopping Imatinib: Should We Worry?
July 30, 2014, Medscape

Treatment-Free Remission by Tyrosine Kinase Inhibitor for Patients with Chronic Myeloid Leukemia
July 8, 2014, JSciMedCentral

Treatment-free remission (TFR) following nilotinib (NIL) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP): ENESTfreedom, ENESTop, ENESTgoal, and ENESTpath.
June 2014, 2014 ASCO Annual Meeting

New Criterion for Restarting Therapy in CML
January 8, 2014, Medscape


Novartis provides update from treatment-free CML  trial      
September 23, 2013,  Zenopa


Stopping Dasatinib and Nilotinib Explored in Chronic Myeloid Leukemia
July 6, 2011, Oncology Practice

                      See also The French trial called STIM (Stop Imatinib)

                            
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