CML Educational Program – ASH 2012

CML Educational Session

Speakers:            Susan Branford, David T. Yeung and Susan Branford,David Marin, MD, Francois Xavier Mahon, MD

Monitoring after successful therapy for chronic myeloid
leukemia – Susan Branford

Susan Branford pointed out the importance of continuous monitoring for patients on TKI’s.  She stated that early responses to treatment is beginning to become just as important as the achieving of early hematological and molecular responses and that once patients achieve their 18 months milestone on treatment they need to be continuously monitored.  Even though it is rare for a relapse to happen after 18 months of successful treatment this is rather dependent on continued adherence to therapy. At this point it is not clear how long monitoring should go on, it is clear that continuous monitoring allows our treating physicians to ensure that patients continue to adhere to therapy additionally the monitoring is very important for future stopping TKI trials as patients who are eligible for these trials must be able to fit the criteria of achieving and maintaining a very deep molecular response for at least a few years.

Monitoring disease response in chronic-phase chronic myeloid leukemia: the age of molecular assays? David Yeung and Susan Branford

This talk asks the question that if a patient has a relatively straightforward presentation of CML can a patient be safely managed, monitored through just peripheral blood?  The answer is yes as long as the patients hits their treatment milestones.  This is a good option when we think of patients who might be elderly and bone marrow aspirates may be very difficult for them.  However, should patients not meet treatment milestones then cytogenetics will have to be done in order to rule out additional chromosomal abnormalities.  The caveat in all of this is that all molecular monitoring on peripheral blood must be done at a well qualified lab that has been standardized to IS specifications.

Initial choice of therapy among plenty for newly diagnosed chronic myeloid leukemia – David Marin –

TKI’S IN CML – the gold rush!  The main objective of Dr. Marin’s presentation was to review how each drug that is currently available for treatment of CML can be best utilized for individual patients.

Dr. Marin started his presentation with an overview of the drugs available and then spoke about the difference between the molecules and spoke about a potential reason for the difference in side effects felt between the drugs.

He showed a slide showing the target Kinases for the 5 TKI’s  – explains in part the different side effects of these drugs example IM PDGFR explains some of the side effects of IM.

Marin pointed out that 30-50% of patients who fail IM achieve CCyr with Nil & Das. However, there is no study comparing the three drugs head-to-head at this time -meaning there is  no clear survival benefit for the new drugs over imatinib. Discussed the Hammersmith study.  Covered ENEST nd study looked at Dasision trial spoke about the advantages and disadvantages of IM.  Nilotinib is perhaps better tolerated. He stated that the disadvantages of nilotnib include complicated dosing, emerging side effects and referred the audience to view poster 1679 & 914 for more information.

Dasatinib – better tolerated than IM, once a day better outcomes, disadvantages Pleural Effusion and emerging side effects poster 3770 in session III.  PFS is the same in patients with CCyR regardless of depth of molecular response Druker et al NJ 2006, PFS same Marin et al Blood 2008, MD Anderson Jabbour blood 2011,

Maybe 3 log reduction MMR is the mistake? The real question what is the additional reduction in the transcript level that confers survival 8 year probability of OS EFS, Marin et al JCO 2011 when we look at the time line there is a different aspect and  we can clearly identify survival benefits for these patients.

But, he hypothesized if the objective of drug treatment should be CCyR(?)  and if so, which is the best drug?

In the end Dr. Marin stated that the best drug for the patient is the one that helps the patient achieve the milestones of treatment and preserve a fairly reasonable level of quality of life.  He stated that he felt that since there is no yet discernable advantage with either of the TKI’s then perhaps in the case where money/cost is an issue, Imatinib is the answer.  However he prefers to start patients on either Dasatinib or Nilotinib then change therapy if needed.

Dr. Marin’s presentation provided a good overall view of what is currently available to treat CML and gave good food for thought to help physicians determine which drug is better suited to which patient based on patients potential co-morbidity or goal for managing their CML.

Is going for a cure in CML possible and justifiable? – Dr. Francois Xavier Mahon

Dr. Mahons presentation started with the thought that while the word ‘cure’ may mean the absence of disease, symptoms and all other signs without treatment, it just may be that for CML we cannot ever say for sure if we have eradicated the last CML stem cell.  He reviewed the early trials of patients who had successfully stopped interferon, before the era of imatinib.  He pointed out that it was in only very rare cases that patients had late relapses years after stopping therapy.

He reviewed all the results of the STIM trials to date, which we will not cover here but remind our readers that this trials have been on going since 2005 when the first 14 patients stopped imatinib treatment and roughly 7 of these patients remain in stable molecular response off of treatment.  So there is a good base of data that is being built slowly that makes the reality of stopping trials more important.  However Dr. Mahon feels that MR3 is not a reasonable goal and that patients who achieved and sustained deeper responses such as 4.7 to even 5.5 for at least a few years have better success at stopping therapy.

Mahon reviewed all the possible things that one can do to help a patient achieve the best possible response and achieve eligibility to stop treatment; either add interferon to Imatinib, use either Dasatinib or Nilotinib earlier up front or explore new ways to target the leukemic stem cell.

We feel that Mahons presentation, as always, offers new hope and provides sound rationale to individualize treatment protocols that help each patient achieve the best response possible.  Additionally his message sends a powerful example to patients about being adherent to therapy and that maybe CML treatment isn’t going to be the life long approach that we once thought it was going to be.

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