13 replies to this topic

[Tom1278]

Hi everyone,

A few weeks ago, I had my 15 month tests done.  I went to a new doctor -- who is a CML specialist -- because I had a lot of problems with my old one.  I'm really happy with the new doctor.

My history was (on 400mg Gleevec):

Diagnosis: FISH 97%, PCR IS 145%, 2% blasts, no spleen enlargement, WBC 140k

3 months: FISH 71%, PCR IS 39.7%

6 months: FISH 4%, PCR IS 5.7%

9 months: FISH 1.2%, PCR IS 4.6%

12 months: FISH 0.8%, PCR IS 2.3%

The crux of my issue was that at 12 months my FISH was 0.8% and PCR was at 2.3%, so it was unclear if I had a CCyR.  My old doctor was of the "everything's great!" club because everything was going down, albeit slowly and below the "optimal" rate.  I certainly wasn't on track for a MMR by 18 months.

My new doctor agrees that my results were sub-optimal and wants to see me have a faster and deeper response, mostly because of my age (34) and the fact I'll have to manage this potentially for 50+ years.  So, she ran the whole set of tests, and I had a BMB to see what was going on in the marrow.  She posited I might be a high metabolizer of Gleevec, which is why my test results have been going steadily down but not at the ideal amount.  [Note: Apparently Novartis isn't offering the Gleevec blood levels test anymore.  She said she tried to order it for a patient last year and wasn't able to.  I guess this is to push more people to Tasigna!]

The good news:  The PCR went down to 0.71% (2.1 log reduction from 100%, 2.3 log reduction from diagnosis) and the BMB confirmed CCyR -- no evidence of residual leukemia. 

The bad news:  It doesn't appear I'm on track for the MMR at 18 months.  And, the mild anemia I had in months 1 to 6 has returned.

I have a follow-up visit on Monday to discuss whether or not to change my treatment regimen.  As previously discussed at the initial meeting, the options are: (1) stay as is, (2) increase Gleevec dosage, or (3) move to Sprycel.  I have very few side effects on Gleevec, so I'm not inclined to switch drugs.  I'm also concerned about increasing dosage because of the mild anemia -- I don't want it to get worse.

I'd love some feedback on my situation to prepare me for this visit.  Thanks!

[Tedsey]

Since when is the goal of MMR at 18 months?  I am not even sure MMR is a certain goal anyway in CML.  I think it is more like icing on the cake where PCRU is the cherry.  I have not read that the expectation of CCyR at 12-18 months has changed in the NCCN guidelines, http://www.nccn.org/...index.html#/44/.  I believe CCyR by 18 months is still on target.  It appears you are moving along as expected, and that is good.  I think with the more powerful drugs available, some oncologists feel movement to MMR or PCRU should be faster (but as far as I know, PCRU still only happens in about 40% of the CML population).  I don't think there is anything out there that supports a person's age being part of the equation (but in our culture, bigger is better, faster is more--even without any real support of it).  I was also considered young at dx.  But my age was never considered in my treatment plan.  Dose reduction over the long haul appears to be most logical, especially if you have held a deep response for years at a standard dose.  I don't understand the desire to get you to MMR faster because you have 50+ years ahead on TKIs.  I wonder what her logic is.  No one has the power of precognition as far as I know, (although I have heard of a few oncologists who treat CML trying).  Even if you reach MMR fast, it doesn't mean you could ever go off medication.  So, God wiling you live another 50 years, unless there is a cure or different and better therapy, you would still be taking a TKI.  In past studies (ex. STIM) most people "relapse" when they go off medication.  So, I am unclear what your CML specialist means. 

I have also dealt with anemia.  This is not uncommon with TKIs or CML.  Glad yours is only mild.  Hope you are not feeling its effects. 

It took me 18 months to reach CCyR and 3 years to reach MMR.  I am still very alive and kicking.  But of course, I wish you speedier healing because it has the magic effect of making people more hopeful quicker.  In my humble opinion, it sounds like you are on track and doing well.  I would just stay the course.  But I am sure others will chime in.

Tedsey 

Please don't take my response as being sarcastic.  Although, I am sure it is unintentional, it is a pet peeve of mine when oncologists plant seeds of fear in their patients by creating their personal treatment goals for them without checking the data.

[August1]

Hi Tom,

Funny, I was going to create a post on this too. I was also diagnosed about 15 months at the age of 42 and am hovering right around CCyR.

I agree with Tedsey. Based on my understanding CCyR at 18 months a more realistic target. If someone doesn't hit that they may want to consider trying another drug. Of course CML is not exactly the same thing from person to person.

Do you know what fusion transcript you have? I have P210 e13a2 which has been shown to have a slower response to imatinib than those with e14a2. In spite of this, there is no difference in terms of overall survival, it just means that Gleevac alone is not the perfect drug for everyone with CML. (For anyone interested: http://www.ncbi.nlm....pubmed/19713230).

Related to my history: I was on Gleevac for the first 12 months of treatment and had a "good" response like you. My PCR was 1% after 12 months but my docs were happy overall because I was moving in the right direction and other counts looked good. I did decide to try Sprycel (mostly because of Gleevac side effects). I took a 15-day break from treatment (my PCR shot up to 3.7% during that time) but I am now around 0.6% after 14 months of treatment.

My oncologist also recently mentioned my age (now 43) and expressed some concern about keeping CML in check for decades with TKIs. I can appreciate his concern. He is a great doc but he has also been doing this for over 25 years and was treating CML for many years prior to the advent of targeted therapies. Back then it was a much different story.

If the Gleevac is contributing to your anemia it doesn't seem like increasing dose would be a good thing. It seems like you're doing pretty well on Gleevac  but there are certainly other more potent drugs available. Of course we all respond differently and each drug has it's own side effects. Just need to find which one is best for you.

Take care,

[Tom1278]

My doctor fully acknowledged that there is no consensus on whether or not these deep molecular responses lead to long-term better outcomes.  However, if there is potentially a 1-2% lower chance of disease advancement with MMR as opposed to CCyR, and then potentially a 1-2% lower chance with PCRU vs. MMR, then it makes perfect sense to me that someone with a 50+ year horizon should aim for a deeper response than someone who is, say, 70 years old and may have an (on average) future life expectancy of 10-15 years.  It's all about probabilities, and if you have to live with a disease long-term, it's best to drive the probability of advancement to as low as possible as quickly as possible.

Both of my doctors said they prefer Gleevec for young patients like myself because it has much more safety data on long-term usage than the newer TKIs.

I have the "typical" breakpoints, and my disease at diagnosis was low-risk (no spleen enlargement, low blast %, platelets high normal).  That's why she thinks that I might just metabolize Gleevec a bit faster than normal.

I'm leaning towards perhaps requesting an increase to Gleevec 600mg just to see if that will kick the CML down to MMR or below.  I'm only concerned about the mild anemia.  I have some minor side effects, like exercise is a bit more tiring, for example.

[Tom1278]

I should probably mention the anemia stats at 15 months:

RBC 3.69

Hemoglobin 11.2

Hematocrit 34

[Tedsey]

Hi Tom,

I also had P210 e13a2.  However, it didn't show up until six months after diagnosis with another onc and another lab (unusual because it normally shows up at dx).  Anyway, I was wondering where you, (or your doctors), learned that people with the P210 e13a2 breakpoint were slower to respond to imatinib.  I would be interested in reading more.  At the time I had it, there wasn't much on it.  It would have been nice to know this when I felt depressed I was moving so slowly.

Take care,

Tedsey

P.S.  I will be diagnosed 4 years this Thanksgiving.  I considered myself a turtle compared to many on the board, but I still made the CML "milestones" so to speak.  MMR and PCRU seemed to come out of nowhere (my last 2 PCRs were negative).  Before, I was stressing that I may never get a deep response.  Now, I stress that I won't keep it.   I think the total goal is to have proof the disease is not progressing.  And CCyR and holding it is.  However, when there is better to achieve (MMR or PCRU), it just dosn't feel good enough--even if 1-2% only translates to 2 weeks to a month more of prospected life.  Good luck!

[Trey]

The difference in response between e13a2 (b2a2) and e14a2 (b3a2) is insignificant.  The study information on this is based on very small numbers of patients, and many variables.  So I would not trust the data.  I have both e13a2 and e14a2, and was the poster child for speedy response to Gleevec. 

The goal for CCyR is 12 - 18 months.  An 18 month CCyR is considered at the low end of optimal.  So a 15 month CCyR is right on average. 

It is interesting to hear the Onc say she thinks you metabolize Gleevec too fast.  If true there are two things you should do: 1) split the dosage taking half dosage twice per day, and 2) increase dosage to 600mg (split 300mg twice per day).  Most of us have or had anemia to some degree, and many have severe cases.  Mild anemia is to be expected, and should not deter treatment changes.  Split dosage may help, so increased dosage may not be such an issue.  In 8 years of taking Gleevec I have almost never been free of "anemia" as defined by blood counts.  But I have plenty of energy and am unaffected by it.  So it is a matter of degree.

Novartis stopped the Gleevec Blood Level Testing because the FDA accused them of creating questionable tests to sell more drugs.  I believe the test was useful in some cases.  But the FDA screwed this up.  So now only research labs do them.

[Tom1278]

Hi Tedsey,

I didn't know anything about the breakpoints until Wespahr posted it.  I have e14a2 (b3a2) and only that one.

Once I found out I had CCyR, I had a huge sigh of relief because I know deep down that is the most important milestone.  I still want to get those deeper levels... call me an overachiever

It is interesting how much disparity there is among doctors about how deep and how fast responses need to be.  I've read some materials from Dr. Cortes and other specialists that advocate quick and deep responses and, if you don't get them, moving to other drugs.  Some, like my new doctor, prefer to start folks on Gleevec because (1) it has much more data on long-term usage and (2) it works just fine for 60-70% of people.  I think treating CML is more art than science sometimes.

Tom

[Tom1278]

Thanks Trey!  I'm going to advocate for the increase to 600mg.  I believe you did the same thing.  Did you notice an appreciable difference in your side effects?

Also, at what point did you advocate for trying dose reduction back to 400mg?  (Or below, I think you might be at 200mg now?)

Best,

Tom

[Trey]

I started at 400mg and did well, but went to 600mg after a couple months just for grins.  I achieved very fast MMR (3 months) and PCRU (less than 8 months).  Went back to 400mg after only a couple months on 600mg, which sent my counts to low levels and caused increased fatigue.  Everyone responds differently.  I could not handle the 600mg and really did not need it.  But some teenage girls need 800mg Gleevec and tolerated it well.  I went to 200mg only after 3 years PCRU, and have been on 200mg about 4 years.

[Tedsey]

CORRECTION:

I think after 4 years I forgot some of the details surrounding my dx and shortly thereafter.  I'll conveniently blame it on the TKI.  Why not?  It's a good scapegoat.  Anyway, I was diagnosed with p210 (b3a2).  However, it was p190 (e1a2) that was detected six months later, (not at diagnosis).  p190, I think, normally shows up at dx.  In my case, I think the lack of detection was due to the less sensitive machinery at the lab of the 1st onc who treated me.  So, likely it was always there, but undetected. 

I also reached CCyR 12 months after dx (not 18 mos.), but on 100mg dasatinib.  I switched to dasatinib after 9 months on imatinib mostly due to life threatening pancytopenia and hemorrhaging on imatinib.  Dasatinib, so far, turns out to be a good match for me.  OK, corrections made. 

So, speaking of switching to 600mg Gleevec above, if you tolerate it well, I agree with Trey, to go for it if you want to try for a deeper response.  We are so lucky there are other drugs for us to take and now dosages are being more seriously explored.  One of the TKIs or dose adjustment usually does the trick.  

Clearly, a diagnosis of CML falls into the category of "The Worst News Ever".  It turns your whole world upside down and changes your life perspective forever (because it is one of those diseases no one can clearly blame on you, it just happens).  This is especially disturbing when you are younger.  Younger people who get cancer are robbed of the illusion that they will live forever (they are supposed to believe this when they are young).  It leaves a huge dent in their social-emotional development as they now face what people decades older do.  But I like to believe those of us who are not elderly will still make it to old age, (I am getting older, so 50 doesn't looks so ancient anymore--LOL).  I hope by the time we reach old age, we will have greater personal strength and wisdom about the value of human life to pass on (at 97, my grandmother, has always lived a healthy and sheltered life--I cannot say I am not jealous of her health, but she has always had major limits to her empathy and wisdom--I am a firm believer that you have to "have it happen to you" before most of us can change for the better, but of course it is all about how much you are open to learning when it does "happen to you").  Anyway, hearing peoples' CML journeys helps a lot (it always helps me to see a story like mine, and since age seems not to have anything to do with how we respond to treatment, I value advice from all of us, young and old). I have had a few years of bumps in the road before I got to where I am now.  As I have said previously, I have reached a deep response and feel very well.  And I am scared to lose any of it, so the anxiety never fully goes away, but I cope better (don't skip your pill!).  

I wish for all of us to have solid proof of no disease progression (slowly or quickly) indefinitely--until there is a cure, of course.

Best of luck,

Tedsey

[Tedsey]

Hee, hee, I responded to myself.  Actually, I meant to for the correction.  However, I think I goofed in addressing Tom before when I mean to address Wespahr.  Thanks Tom for being so nice.  And sorry guys!

[Antilogical]

1.  ANEMIA:  The first sign of trouble for me was a sudden onset of anemia.  That may or may not resolve itself.  Mine returned to normal for a while, but now tends to be a slave to peer pressure when my immune system tanks.

2.  POSTER CHILD?  Trey: Must.See.That.Poster!!! 

3.  WORST NEWS EVER:  I am not "young", as I am within spitting distance of retirement.  Nevertheless, I still like to think I'll live forever.  WITH CML.

--Sandy.

[Tom1278]

Well, just got back from the doctor.  She was very happy with the 15 mo results and we aren't changing anything.  She'd like to see me have the MMR by 24 months, and if I don't hit that, we will re-evaluate drug choice/dosage at that time.