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The European Hematological (EHA) Congress of 2011 - What has me so excited! - Summary Report


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#1 cherylannes

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Posted 29 June 2011 - 07:50 AM

As Promised:

The European Hematological (EHA) Congress of 2011 - What has me so excited!

The EHA congress gathered together some of the most influential opinion leaders in CML from around the world.  It was very good to see them all together and to hear them present, ask questions and be so involved as they are in CML.

The Friday Satellite Symposiums are usually all sponsored by Pharma and usually are good sessions that provide background and an update on the trends with regards to treating and managing CML.

Although my departure was late leaving from Montreal on Wednesday night, I did arrive just in time to attend the Novartis symposium, which I reported about.  The key learning points from the presentation were that Nilotinib (Tasigna) appears to be very effective in helping patients achieve MMR and subsequently CMR when used either as first line in newly diagnosed patients and as second line therapy for patients who are resistant or intolerant of Imatinib (Gleevec).  We also learned the importance of standardizing molecular testing, such as PCR.  The main reason for this is so that more centers can possibly participate in the "stopping TKI" trials that will become more available in a short time.  This was an excellent segue into Dr. Mahon's talk which precisely spoke about the success of the stopping TKI trials.  I do refer to it as a success when you consider that 40% of the patients are able to stop their TKI and have not had a recurrence of the disease for quite a number of years.  Importantly, these patients are being followed very closely once a month with PCR monitoring.  The other important fact is that no patient who stopped the trial and had a recurrence developed a resistance to Imatinib when they re-started the drug and nearly every patient regained the same response they had prior to stopping.  I can tell you that I spoke to him about this and he even told me that he has a few patients who re-gained CMR 4.5 and held it for a couple of years and consequently re-stopped their drugs and have not had a recurrence.  You will notice that I am using the word recurrence here and not relapsed.  When I spoke to Dr. Mahon he said we must use the word "recurrence" as the word "relapse" implies that patients have a more aggressive form of the disease and in fact they do not.  We do not have a good explanation for why some patients can stop their drug and this is something that is being investigated.  One theory that is being thought of is that some patient's immune systems regain control and are able to keep the BCR ABL transcripts down when they do recur.  Remember that 70% of the normal, non-CML people in this world will test positive for the BCR ABL transcripts at any given time on PCR.  However, they will not go on to develop full-blown CML.  This tells us that there is something going on that allows us to fight back this disease.  So, it is not impossible that there are more of us like this.  Dr. Mahon said that there really is no difference in age or gender of people who can stop the drug and a slight benefit may be conferred to patients who have low sokal score risks and have been pretreated with IFN (Interferon).

In the Bristol Myers Squibb symposium, we learned that Dasatinib equally provides first line and second line treatment benefits just as Nilotinib does even though the primary end points in the trial were different.  In the Nilotinib trials, primary endpoints was MMR, while primary end points for the Dasatinib trial was confirmed CCyR (confirmed being on two separate times).  But, we also saw in the 24 months follow up with Dasatinib, that patients did go on to achieve MMR at a very high and very comparable rate to Nilotinib.  This is great news for patients as we all have our biological differences and we need as many choices as possible.  When it comes to understanding our molecular responses and we receive our results from our health care team we have a new question to ask; are our results based on a 4-log reduction, which is CMR 4, or 4.5 log reduction, which is CMR 4.5, or even a 5-log reduction, which is CMR 5.  For the purposes of the stopping trials, I should point out that Dr. Mahon's lab reports at a 4.5 log sensitivity but based only on 20,000 transcripts, so patients who achieve and sustain a CMR 4.5 in his lab and hold it for 2 to 3 years become eligible for the stopping trial.  Very importantly we can see that Tasigna and Sprycel both offer great options for patients to achieve deeper level of responses in a shorter time frame.

From the CML Education session on Saturday, we learned the latest information on what is being done to eradicate the Leukemic Stem Cell Clone.  Dr. Holyoake talked to us about several approaches, many of which are in clinical trials.  Importantly many of the approaches preserve healthy stem cells and target only the malignant stem cells.  Additionally, some of these trials are pairing Imatinib with drugs that are already available on the market, such as Zileuton an asthma drug and Hydroxychloroquine an anti-malarial drug.  She also spoke about a drug called FTY720 (Gilenya) which is actually a drug being marketed by Novartis for MS.  It is exciting that these drugs are available and that our doctors can access them to get more of these trials underway.

Dr Hochhaus reminded us that the use of IFN should still be considered.  He has patients who have been off of TKI's for several years and are being maintenance on a low dose of Peg IFN.  This represents a great quality of life for these patients, imagine having only to take one shot every two weeks with little to no side effects?  All the rest of the time, you can completely forget about your disease.

Dr. Kantarjian reminded us that in order to ensure that we can maximize the number of CML patients to achieve a longer life and a relatively good quality of life, the rules should change a bit when it comes to classifying sub optimal responses and failures.  He thinks the new rule should be if a patient hasn't achieved a CCR by six months, change to another drug quickly.  The reason being that the chances of achieving a CCR after this time become more difficult and obviously we have many choices of drugs to chose from at this time, so why jeopardize patients chances of achieving a CCR which translates to significantly improved overall survival and progression free survival.  I agree with him on this point as patient's who rapidly achieves CCR has a better chance of going on to achieve MMR and perhaps CMR and then become eligible for a stopping trial.  So, I think as patients we should push ourselves further and try to see if we can improve our own chances of achieving this level of response.

At the clinical session on Saturday we learned about the 24 months follow up for Tasigna front line and saw very impressive response rates for patients achieving MMR.  We know now that patients who achieve a deeper level of response significantly improve their chances of disease progression free survival and overall long-term survival.

Additionally we learned that Bosutinib is an additional choice that hopefully will become available to us shortly.  We have to understand that with this drug there were some unfortunate areas where some of the investigators did not have experience with the drug and when patients experienced the diarrhea that happens in the first 5 weeks of this drug therapy, they prematurely stopped the drug.  Patients who persevered noticed that their diarrhea significantly improved after the 5 weeks and are not being bothered by it, but importantly they saw their response to the drug improve.  From my own perspective, I am aware of a few patients on the drug and they have done exceptionally well.  My information also takes into consideration a patient with a very stubborn form of CML who finally achieved a complete cytogenetic response and even a Major molecular response (MMR) and another patient who has achieved a sustainable CMR.

We learned that Kinase Domain mutations are more frequently detected in patients who are very suboptimal responders such as only achieving a complete hematological response, or a partial cytogenetic response.  Patients who failed to achieve the treatment goals as defined by the ELN chart were more likely to harbor a mutation (57%).  However in the suboptimal responders category 21% of patients were likely to harbor a mutation.  However patients who only achieved a complete hematological response without a cytogenetic response of any kind were at a very high risk to have a mutation (71%).  So, this proves to us once again, the importance of being monitored very closely and very early in disease treatment so that our health care team can respond quickly and help us to achieve a better response level.

A very exciting session on Saturday profiled some new research that is looking at additional test that can possibly be done up front at diagnosis that my help Doctors determine the best drug to use front line on a patient to maximize the best results in a quicker time frame.  Dr. Sarut Mostijoki presented data that looks at the amount of CML stem cells in bone marrow aspirate and correlated it with trend to response to treatment and the probability of hitting the appropriate responses with in the appropriate time frame.  This is a very important step forward, particularly for patients who have financial caps on their drug programs.  This may help patients get on the right drug quicker rather than spend money only to find out 6 months to a year later they need to switch drugs.  Nothing is 100% foolproof, but at least this might provide a logical argument and rationale for using one of the newer drugs in a front line setting.  Even though they are indicated for that use in the United States, soon in Canada, our insurance providers may not always reimburse it.  We need stronger arguments and this one may help us.  Additionally the biology session on Saturday provided more insight into the interesting development of CIP2A and it's role in CML.  Understanding how CIP2A inhibits PP2A, which is a negative, we do not want to inhibit PP2A provides a potential new target that may help some patients with a more stubborn form of CML achieve a better response rate.  The other interesting research was the prognostic value of looking at the BCR ABL fusion transcripts.  Patients with a b3a2 transcript achieved MMR in a shorter time frame than patients with a b2a2 transcript.  Again this may make the case for starting a patient on one of the newer TKI's rather than just arbitrarily starting someone on Imatinib and waiting to see what happens.

The new EUTOS scoring system shows that it was helpful in correlating risk factors with outcomes, but importantly this is because this scoring system was specifically designed to take into consideration the current drugs that we use to treat CML.  Therefore a patient who might be deemed intermediate to high risk on the SOKAL scoring system, may not be a deemed to have the same level of risk on the EUTOS scoring system and this is because we know that these new drugs are much more effective at treating the disease.  The SOKAL scoring system was designed to establish risks based on the use of older chemotherapy and IFN, these drugs were not as effective in managing the disease, so a patient could be at a higher risk to have their disease progress, this is not the case at this time.  This message really hit's home more effectively when we consider that in the update on the stopping TKI's from the Bordeaux France group, we have seen that even patients who were sub optimal responders on Gleevec or even resistant are now being enrolled in the stopping TKI trial.  This is very exciting.

Importantly on Saturday morning there was a patient advocacy session that covered the topic of adherence from many perspectives, but importantly the perspective of the patient.  The session started off with Dr. D. Marin from Hammersmith reviewing his study from 2008 the MEMS trial.  In this study patients were given their Drugs (Gleevec) in a special bottle that was rigged to record how often the bottle was opened, so effectively it tracked how many times during a month a patient actually took their drug.  The results showed a strong correlation between the patients who took their drugs as prescribed and the level of response achieved.  Those who took the drug consistently achieved a deeper level of response.  Giora Sharf reported form the perspective of the patient and provided data from a pilot survey regarding adherence.  The preliminary results showed that patients may either intentionally miss their drug; i.e. I am going out with the boys tonight and Ii may have a few beers and I know I shouldn't drink when I take my drugs, I want to be like "one of the gang" so I will skip my drug tonight.  Or, my daughter is getting married and I will be in all the pictures and I do not want my eyes to look puffy, so I will take a drug holiday".  Patients may also miss their drugs un-intentionally; they just forget, eat too late then cannot stay up to fast (Tasigna).  Packaging may also be an issue with older patients as breaking through the blister packs, and childproof packaging is difficult when one has arthritis.  During the survey patients were interviewed about if they would like to receive electronic reminders to remind them when to take their drug.  The response was "no", patients do not want to be patients and they do not want to be reminded that they are patients.  The overall message of the presentation is that everyone in the healthcare team plays an important role in the adherence issue, it is not just the issue of the patient.  Doctors should have more honest up front discussions, as well as nurses, explain what happens even if you miss two doses a month.  Pharmaceutical companies should look at better design with regards to packaging and finding better formulations to help make the drug regimen easier to manage.  Improving adherence requires a multidisciplinary approach.

The key messages for patients from the EHA congress are 1.) A deeper response achieved in shorter time frames from starting the therapy significantly improves progression free survival (PFS) and therefore significantly improves Overall Survival (OS) 2.) MMR and in particular CMR are the new goals to achieve in treatment therapy particularly if we want to be in the group of patients that may one day be considered to be enrolled in the stopping TKI drug trials 3.) There are additional tests that can be done up front at diagnosis that provide more information to our doctors that will help them guide us to the right drug in order to maximize our chances at achieving a deeper level of remission 4.) We have a wide range of drugs to help us maximize our chances of getting healthy again and staying healthy: Imatinib, Dasatinib, Nilotinib, Bosutinib, Ariad, Omacetaxine add to this some very interesting drug trials that pairs some of these drugs with drugs that are currently being marketed for other indications and we can see how rapidly the research is progressing for us.  5.) A quote from Dr. Mahon "If you want to stop taking the drug, all you have to do is be adherent to the drug" but to this I would add you have to be vigilant, you have to know and understand your level of response and talk to your doctor about your level of response on each visit - know your score!

Among the major pharmaceutical companies involved in CML, the over all theme was improving patient outcomes and responses with TKI therapy.  While all companies had very good slogans that were attractive and exciting, the advertisement from Novartis stood out very clearly: "We're on a mission to change the path in Ph+ CML.... And we'll stop at nothing".  I like the sound of that!

Attending this meeting was one of the most important events for me this year. It is very exciting to see the innovativeness of the European based researchers and doctors.  I am looking forward to ASH and tracking the progress of much of this work as it makes it way from out of the labs and to the patients.  Exciting times ahead.

Cheers,

Cheryl-Anne



#2 TroyLynn

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Posted 29 June 2011 - 08:59 AM

Well done, thank you for the report, it made my day. -Troy-



#3 Marnie

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Posted 29 June 2011 - 10:34 AM

Thanks, Cheryl-Anne.  Very exciting stuff, and timely for me, as I got my PCR done yesterday and will meet with my onc next week to go over results.  Your summary actually made me excited about getting a BMB!

Marnie



#4 SunNsand

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Posted 29 June 2011 - 02:11 PM

"Patients with a b3a2 transcript achieved MMR in a shorter time frame than patients with a b2a2 transcript." - This statement doesn't excite me much



#5 Marnie

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Posted 29 June 2011 - 02:26 PM

Yeah. . .me too.  This is pretty old news, however.  At least it explains my slow response.  When I pointed the research out to my doc last year, he wasn't concerned.  To him, speed isn't hugely important, as long as one continues to trend in the right direction.

Marnie



#6 Trey

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Posted 29 June 2011 - 04:39 PM

The difference between b2a2 response rates and b3a2 response rates is fairly insignificant.  This is a matter of measuring the data with a micrometer after having sliced it with an ax.  In my own case I had both b2a2 and b3a2, and my PCRs show that both decreased at the same rate, and both went to zero at the same time (just over 6 months).



#7 Marnie

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Posted 29 June 2011 - 05:15 PM

I think it probably depends on a lot of variables.  I'm still waiting to get to zero after more than 2 years (getting pretty close, though).  Another woman in the area got there in 2 or 3 months.  I have b2a2.  She has b3a2 (I think I got that right).  On the other hand. . .can't really compare our numbers because I was diagnosed with a much higher WBC. . .

I believe that b2a2 responds more slowly. . .but I also believe my doc that the speed doesn't matter all that much as long as you are moving in the right direction.  Maybe that's too simplistic, but it makes sense to me.  Not to say that I haven't had my moments of stress because I'm a turtle (or is that a slug??  Tedsey??)

Marnie



#8 Trey

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Posted 29 June 2011 - 08:48 PM

The b2a2 vs b3a2 issue is only one of many variables when it comes to speed of response.  Most likely the other variables are more significant.



#9 CallMeLucky

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Posted 30 June 2011 - 01:08 AM

For what it's worth, I only had b2a2.


Date  -  Lab  -  Scale  -  Drug  -  Dosage MG  - PCR
2010/Jul -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 1.2%
2010/Oct -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0.25%
2010/Dec -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0.367%
2011/Mar -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0.0081%
2011/Jun -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0%
2011/Sep -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0.00084%
2011/Dec -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0%
2012/Mar -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0.004%
2012/Jun -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0%
2012/Sep -  MSKCC  -  Non-IS  -  Gleevec  - 400 - 0%
2012/Dec -  MSKCC  -  Non-IS  -  Sprycel  - 100 - 0%
2013/Jan -  Quest  -  IS  -  Sprycel  -  50-60-70  - 0%
2013/Mar -  Quest  -  IS  -  Sprycel  -  60-70  - 0%
2013/Apr -  CUMC  -  Non-IS  -  Sprycel  - 50 - 0.036%
2013/May -  CUMC  -  Non-IS  -  Sprycel  - 50 - 0.046%
2013/Jun -  Genoptix  -  IS  -  Sprycel  - 50 - 0.0239%
2013/Jul -  Genoptix  -  IS  -  Sprycel  - 70 - 0.0192%
2013/Jul -  Genoptix  -  IS  -  Sprycel  - 70 - 0.0034%
2013/Oct -  Genoptix  -  IS  -  Sprycel  - 70 - 0.0054%
2014/Jan -  Genoptix  -  IS  -  Sprycel  - 70 - 0.0093%
2014/Mar -  Genoptix  -  IS  -  Sprycel  - 100 - 0.013%
2014/Apr -  Genoptix  -  IS  -  Sprycel  - 100 - 0.0048%
2014/Jul -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2014/Nov -  Genoptix  -  IS  -  Sprycel  - 100 - 0.047%
2014/Dec -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2015/Mar -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2015/Jun -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2015/Sep -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2015/Dec -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2016/Mar -  Genoptix  -  IS  -  Sprycel  - 100 - 0.0228%
2016/Jun -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2016/Sep -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2016/Dec -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2017/Mar -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2017/Jun -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2017/Sep -  Genoptix  -  IS  -  Sprycel  - 100 - 0%
2017/Dec - Genoptix  -  IS  -  Sprycel  -  100 - 0%
 

 


#10 SunNsand

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Posted 30 June 2011 - 07:16 PM

I made my earlier grumpy comment after having a few bad weeks. I do have these two bad boys but they are acting independently of each other. One will drop in the basement where it belongs and the other goes upstairs where it's not wanted. The next time they flip-flop. I guess they just don't want to play together in the basement lol






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