24 replies to this topic

[jenn]

Ok, so we just got back the results of my husbands 1 year bmb and the doctor wants to switch him to Sprycel ????? The results say.. the findings are consistent with cytogenetic remission. I still cant make heads from tails on these tests,  Dr says he has to be 0 detectable @ 1 year and wants to swich drugs. He has very few side effects fron the G so I am reluctant for him to switch. It does say positive for major breakpoint (0.089) in the bcr-abl transcript and is consistant w/ cml. Overall, the peripheral blood and bone marrow show no morphologic involvement by cml.

Dr already sent in the perscription but didnt order the heart test yet ? I feel like expecting 0 at one year is long shot,but Dr says this is the new protocall ?????

Advice please.... Thanks , Jen

[Tedsey]

Jen,

Unless things have changed overnight, and they may have, but I am pretty sure I would have heard, 0% at 1 year (or at any time) is what most of us could only dream of.  Your husband has reached CCyR at 1 year.  That is very good.  It means that the sample of cells from his BMB look totally normal (no sign of CML in the chromosomes).  However, there is evidence of CML seen at the molecular level (the PCR).  But, .089 seems relatively decent at 1 year.  I would love to be closer to that number, and I have been on Sprycel 1 year, (I was dx Nov. 09).  So, I am  not sure I understand your onc's advice to switch your husband to Sprycel.  It appears your husband is doing well on Gleevec.  If his PCR stalls or increases, or he loses CCyR (God forbid), or he has horrible side effects, then I could understand why a drug change would be in order.  Seems like Gleevec is a good fit for him.  It is also tons cheaper than the big ticket item, Sprycel.

The major breakpoint for CML is usually b2a2, it is the most common place where chromosome 9 breaks off (there are different places a chromosome can "translocate", or break off).  I still believe that CCyR remains hoped for at 1 year to 18 months.  Your husband is right on target.  I also think the Sprycel has shown much success and has brought many people to a quicker and deeper response.  But I don't think it brings most to zero.

If the new norm is PCRU, or zero, at one year, instead of stable, I would be doing poorly at 22 months since dx (my PCR is higher than your husband's).  I am not sure where your onc got his info.  I think you are right to question.

All the best,

Tedsey

P.S.  I am not sure how old your husband is, but my onc felt it was unnecessary to have my heart checked before my switch to Sprycel.  I am not sure age is a factor.  And if he does switch drugs, for the record, I feel pretty great on Sprycel.  If it weren't for my CBCs, BMBs and PCRs, I would not know I had CML--except for the mental torture.  For me, the anguish over getting this disease has been 1000 fold worse than any physical pain that comes from the treatment of it.  

[HeatherZ]

I'm with Teds - I think he has made great progress for the 1 yr mark.  This is my 18 month mark and I havn't hit 0 yet.  Hang in there.  I would definitly ask more questions and also challenge the doctor if I felt comfortable with the current treatment and progress.

Heather

[PhilB]

Hi Jenn,

When you husband's doc signed the prescription he wasn't using a shiny new pen with a Bristol Myers Squibb logo on it by any chance?  Or any other signs that he'd just had lunch with their sales rep?

Firstly I would be challenging him very strongly on where he got the idea that PCRU at 12 months was the target for Glivec as in that case there'd be no point in starting anyone on G in the first place as only a tiny percentage get anywhere near that.  This would give him a chance of demonstrating that he's not a moron after all.

Secondly, do you know if that 0.089 is a ratio or a percentage?  If it's a percentage on the International scale (which would be the most usual way of reporting) then your husband is in MMR at 12 months, which is a great place to be, and there is no pressing need to change drugs unless he fancies it.  If it is a ratio, and therefore really 8.9%, or is reported on a scale whereby it is not an MMR then his response is good (because he's CCR), but not great and a change of drugs would be a sensible thing to be thinking about.

Best regards

Phil

[LivingWellWithCML]

You should find out if the onc knows the NCCN Guidelines - he/she better know these by memory!  My understanding is that the NCCN Guidelines are widely regarded as the standard measuring stick for CML treatment response.

BTW, the guidelines are very clear.  At 12 months, if the patient has reached a Complete Cytogenetic Response (CCyR), then the patient should continue with the same TKI at the same dose.  And this should be compared with the PCR results.  If your husband is trending down on the PCR (ratio or percentage is the question, as Phil mentioned), and he is tolerating the TKI, then there is no reason to make a switch.

Also, I'm in touch with another CMLer who is an active runner like I am -- and he's also on Gleevec 400mg (like me).  It took him a full 18 months to reach CCyR, and he ran two marathons during that period of time, so clearly he's tolerating Gleevec quite well.  Your husband reached CCyR faster than he did, so the onc should be very pleased with his response.  It's also worth noting that this fellow eventually reached a Complete Molecular Response (CMR) ... it just took awhile.

[CallMeLucky]

I would like to see the consensus among experts that declare the "new protocol" is to be PCRu by 12 months.

NCCN guidelines don't call for that.

Don't mean to be negative, but sounds like your doctor has been enjoying too many lunches from his pharmaceutical rep.

Personally I wouldn't switch at 12 months given the progress made.  Sprycel is a great drug, but it doesn't come without its share of risks.

[gunner]

Everyday that I live I find more reasons to lose respect for the medical profession.

If they expect to be able to dictate significant changes in therapy without explanation, then they also deserve to be called idiots by us, the unwashed masses. He may see something, but the collective experience and knowledge of those affected seem to find no rational reason for a drug change. And if he cannot share what he sees, then he is ineffective in other ways.

The days of 'trust me, I'm a doctor' went away with the cowboys riding off into the sunset.

[CallMeLucky]

Kind of ironic, we live to challenge their work, by virtue of their work.  LOL

In reality it is only the work of a few that make the difference.  Often the rest are just going based on what they read in a journal, heard at a conference, or sadly, what seems to be happening more and more, what they were told by their pharma rep.

Of course we do not know what the doctor's reasons are.  We hope it is not because the drug company is telling him to.  I think everyone feels the same way however, the doctor should be able, and required, to explain why the change in treatment given the overall good results thus far.

[Tedsey]

You're right Luck, it is an irony.  But it is probably not these goofball oncs that are trying to develop a better treatment or a cure.  It is hard to believe that a pharma rep is not involved in this.  How sad it is when physicians have weak scruples.   

[PhilB]

Call me a naive idealist, but I like to think they're not that unscrupulous.  Just gullible, negligent and/or stupid.

[Tedsey]

If they know not what they do, then they should not practice medicine.  I agree, I think most physicians do what they think is best for their patients.  But narcissism, greed, and lack of a moral compass aside, gullible, negligent and/or stupid doesn't leave me feeling more secure.

Glad we have this sounding board.   

[jenn]

You guys are sooo funny, and thanks so much, as always you all have confirmed what I was thinking. We have an appointment tomorrow to discuss the switch. So... I printed the guidelines for him and will hopefully get a different answer than HE MUST BE @ ZERO (he's Hungarian) lol . What is really bothering me is that to even justify a switch his bloodwork needs to show a lack of response right,he also hasn't even tested for a mutation if that's the case ! And if it is lack of response isn't an increase in Glevac called for first ?  And the heart thing, my husband is 37 w/ an irrigular heartbeat. Dr told him Sprycel may cause water around the heart and he does't need the test.... sigh

What would be an exceptable reason besides lack of response ? OMG.. hope I'm ready for this meeting,he's a pretty big scary man ... I will let you all know what comes of it.

Thanks again

Jenn

[PhilB]

Hi Jenn,

Increasing the dose of Glivec is very much out of fashion nowadays.  All the studies seem to show that switching to another TKI is a much better option if G isn't working out.  The only reasons for switching generally would be:

1. Hoping for better side effects
   
2. Lack of response
   
3. Hoping for better response / personal preference
   

It sounds like you're fine with the existing side effects so rule out number 1.

Lack of response is a tricky one now that T & S have both been approved as first line.  In the old days for someone at 12 months not having MMR was seen as a warning, not having CCR as sub-optimal and not having Partial CR (ie still > 35% positive on BMB / FISH) as a failure.  Now that we are in a situation that if your husband had been diagnosed a few months later the chances are the doctor would have put him on a more powerful drug in the first place, it is reasonable to use a much more aggressive criteria to decide on a change from G.  The problem is that there is no official guidance (that I'm aware of) to say what those more aggressive criteria should be so everyone is making it up as they go along.  PCRU at 12 months is NOT a reasonable criteria to use for lack of response (but see below).  My own personal feeling (and no more than that) is that MMR at 12 months 'feels' about right as a trigger point to look at switching, but you could make a perfectly reasonable case to be more, or less, aggressive than that.

The third category is an interesting one.  If the doctor now starts all his patients on Sprycel say as he considers it the new 'gold standard' then there is a case for his feeling 'this is a better drug so I'll move all my patients to it.'  That's not an unreasonable position to have, but it isn't just his choice so if that is the way he wants to go then he needs to explain it and take into account what the patient wants a whole lot better than it looks like he is doing.  A blanket rule that 'if you're not PCRU then you must change drugs' is wrong.  A blanket policy of telling patients not in PCRU  'You're doing well, but we have a better drug now that may get you a deeper response, faster.  These are the risks, if you do have side effect problems we can change you back, would you like to change?' makes a lot of sense in the new world we are in.

[jenn]

So we met with the doctor today.... He still insisted that the new protocol @ 12 months you need to be 0. I  gave him the nccn guidlines dated dated January 2011, he brushed them off and told me that there are new guidelines that came out in July. I asked him if he had a copy for me, he said NO !

He did breakdown the results of the tests, it seems like when blood is drawn @ the hospital it goes to one lab,and when he draws @ the clinic a different lab and they use different methods reading the results ( this is what dr told us) It looks like his numbers are going up, he was @ .02 in March then .07 in June now .09 so I guess in his own way he is saying that he feels the Glevac isn't doing a good enough job and Sprycel OR Tasignia would be better for him. He said once you reach 0 you are cured !!!! And he doesn't know what other dr's are doing but he will only settle for 0, I think he has good intentions but if he had discussed it another way, maybe saying you are doing well but I think another drug might work better ( like some of you said) Anyway he let us know that he is leaving in January..... so we will be on our 4th Dr in 1 year,each Dr not able to understand the others notes is always fun.

I asked for another PCR because the last results were from the bmb aspirate, just wanted to try to compare because it looks like the PCR #'s are lower than when they use the aspirate ??? I dunno.... So we will meet the new Dr in 2 weeks and if we choose we can continue with him,he will be flying in twice a week to start with. I am excited for the second opinion. So we will continue w/ the Glevac until then...

: )))))

Jenn

[valiantchong]

I think the doctor has good intention as what you said. The present golden rule is to get to 0 as soon as possible but may not neccessary. So if you do not lose anything why not try the second generation drug ? Presently the main direction is the second generation TKIs is now a main stream medication, although myself is on Gleevec. 

[Susan61]

Hi Jenn:   Keep us posted, but know your husband has made very good strides to get to where he is.  I am a firm believer in 2nd and 3rd opinions.  I had a great Oncologist, but he even told me to get more opinions so I could see that he was treating me properly.  I admired him so much, and he retired.  My new doctor is following the same Protocol my other Oncologist did.  It took me almost 3 years to get to PCRU after I achieved my Cytogenetic Response.  Nobody said I was running behind schedule.  He might have some good reason for what he feels, but I also agree with getting the PCR Testing through the blood test like you said.  I would want a comparison with the BMB Aspiration also.

     Please keep us posted with your husbands journey, and what you decide to do.

God Bless

Susan

[Marnie]

Hey, Jenn. . .

This may not be what you want to hear. . .but here's another perspective.. .

I was on Gleevec for a year and a half.  I had suboptimal response. . .very very slow reduction of PCR numbers, then a plateau and a small rise.

I switched to Sprycel, and my numbers have improved dramatically.  My side-effects are pretty miuch non-existent.  I didn't realize how lousy I felt on Gleevec until I switched to Sprycel.

Yes, the cost of Sprycel is astronomical.  Yes, after reading your post, I do wonder if the doc is receiving some sort of benefit from BMS, but I gotta tell you. . .Sprycel has been wonderful for me.

Good luck as you make your decisions.

Marnie

[Tedsey]

First, the onc sounds like a crackpot. Glad you are losing him.

And I don't want to be a dark cloud on all this, and likely if your husband is switched to Sprycel, he will show the miraculous improvement many have.  Nevertheless, I like to believe, that not achieving MMR by 12 months does not translate into a poor prognosis.  I don't believe the stats for Sprycel support bringing most CML patients to MMR by 12 months (I got this info. from the huge insert that accompanies each box).

I have been on Sprycel over 1 year.  I have not achieved a MMR.  As a matter of fact, my last PCR went up a little, although well within the margin of error for the test, it was not a better response than 3 months ago.  If your husband has not reached MMR on Gleevec at 1 year, a change to Sprycel may do the trick.  However, as strong and successful as this drug has been, there are no promises as to how quickly a person will respond.  I would hate for you guys to worry about this.  Believe me, I have done enough of it myself.  I am praying to stay CCyR.  There is some support that says if a person has a sustained CCyR, then MMR or PCRU may not be needed for long term survival.  But, of course, who wouldn't want the "insurance" and more "solid hope" MMR or PCRU brings.  Who doesn't dream of lightening-fast improvement?  If your insurance covers it, it may be worth a try.  You can always go back to Gleevec.

Good luck in whatever you guys decide,

Teds

[jenn]

So we have the results of the PCR....negative.... why does the marrow say .089 I thought PCR was just as reliable  ? BMB done 8/10/11 and the PCR on 9/21/11. We see the new doc on the 5th of October. Looks like no need to switch but will see what he has to say.  : )

[GerryL]

Hi Jenn,

The leukemia cells are more concentrated in the marrow - PCR will always have less as it is spread throughout the blood stream.