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One year on Imatinib, not at MMR.

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Greetings!

I've been lurking and reading about CML since I was diagnosed exactly one year ago at 38 years of age. CML was discovered during a routine blood test,  and my WBC was at 147. My hematology oncologist put me on 400mg of Imatinib on January 31st, 2019.

My peripheral blood counts dropped quite nicely and by end of February, my WBC dropped down to normal levels. On the sixth month, an ultrasound showed that my spleen was back to normal size (16cm down to 10cm). I thought things were going great! Didn't really think about CML except for the side effects of the Imatinib.

However, fast forward to January 2020. My IS Burden % is at 0.73. I met with my hem-onc today and he told me that we have to watch it closely at the 18 month mark. If I don't make it to 0.1% or lower, I may need to switch to a different TKI. What really scared me, is that he is recommending me to a Transplant specialist. He mentioned that at my age, if Imatinib is not giving me the desired results, he may decide to go the transplant route.

I am trying to get a sense of where I am at versus members of this support group. Has anyone experienced a very slow path to MMR?

I did find some posts about members being anxious at 0.2-0.3% at the one year mark. Makes my 0.73% seem like a heck of a lot!

Here are my latest results.

Date  / IS Burden %

1/29/2019 - 134

4/29/2019 - 29

7/29/2019 - 3.3

10/21/2019 - 2.2

1/13/2020 - 0.73

 

Thanks everyone!

Howdy,

I'm not a doctor, but I think you're doing just fine.  I was at about 0.4% at the one year mark and at 18 months made it to the magical 0.1%.

Your doctor seems to be focusing on the negative instead of the positive.  Talk of transplant is for patients who are failing to get control of the CML.  In my opinion and if it's necessary, a change to another TKI should be considered way before transplant talk starts.

"... he may decide to go the transplant route"   I believe that you should have some say as to whether you have a transplant.  A second opinion from a CML specialist would definitely be in order if he insists on you visiting a transplant specialist.

Did you have any other BCR/ABL1 tests done at your last blood draw?  Was your FISH good?

My doc did a BMB at one year and the pathology report was encouraging:  "bone marrow biopsy - normal male karyotype with no evidence of a clonal cytogenetic abnormality".

Kirk

 

Hi,

It's often a good idea to look at treatment guidelines, which you can find here.

https://cmlsupport.org.uk/section/cml-treatment-guidelines-tki

I would normally look at ELN guidelines, but NCCN ones for the USA are broadly similar.

The ELN guidelines would put you in the "warning" category. That's OK. The category you want to avoid is "failure", and even then it doesn't mean all hope is lost it just means that particular treatment isn't working out for you at the moment. 

So what does warning mean? Formally, it means "Characteristics of disease and response to treatment require more frequent monitoring to permit timely changes in therapy in case of treatment failure". Basically, it means it's probably a good time to consider alternative treatments. 

The guidelines go on to say that when failing imatinib, consider changing to any of the other TKIs. It also suggests to ascertain the HLA (human leukocyte antigen) type of you and any siblings. This antigen is a big part of what drives the bone marrow match. The reason it suggests this is not because a transplant is necessary or imminent, it's that if the second-line TKI doesn't work, or the 3rd line etc. then it's best to be ahead of the game in terms of transplant preparation.

However, the chances of ever needing to get to a transplant are small. Not impossible, but small.

What should you do next? If I were you, I'd look at the trendline, as your results are consistently going down. Plotting a linear trend over your results sees you hitting MMR at the end of April. I think I'd stick it out for a while, see how that goes but if the number isn't going down as expected, or rises, consider another TKI. 

For what it's worth, it took me over 18 months to get to MMR. I'm now at MR5, so doing as well as possible.

David.

I am attaching a thread of a couple of us that have not reached MMR at 24 months.  We are very close so it God willing is just around the corner.  Interesting is that we are of similar age (39 in my case) so I think there are cases of younger patients taking a little longer to hit the targets.  The good news in your case is that you are responding to a 1st generation TKI.  If you don't get beyond 0.1 in the coming months studies have shown that a 2nd generation TKI will probably get you there.  If you don't trend closer to 0.1 in the next couple of months I would discuss switching TKI's.  Not everyone responds ideally.  My personal concern is if I were not responding at all or could not tolerate the medication (which does happen).  Hang in there and you probably have good news coming in your next results.  

https://cmlsupport.org.uk/thread/13049/sprycel-lack-response#post-57491

oops forgot to attach thread.

Also I think that discussing transplant after only having been on Imatinib and being under 1.0 is very aggressive.  This should be the last option after many TKI's and possibly clinical trials.  I'm no doctor but there are options out there and this early of a transplant discussion I think is out of bounds.  My oncologist mentioned that they have done two transplants in 5 years across all patients.  Hospital serves Colorado and many neighboring states.  

You are doing great.  There are many, many turtles here - I'm one.  I wasn't quite at MMR at 22 months but these days I'm consistently at .005 or .006.  I just got my PCR and it's 0.007 this time.  I am not panicking and you shouldn't either.  The differences between your .2, .3 and .7 are negligible.  You are trending consistently downward.  If you don't get there ultimately, second generation TKIs most probably will get you over the line.

Although your hem-onc is following guidelines, and as David pointed out, it's not out of line to get the antigen testing done or to be discussing a drug switch with you, bottom line is:  he scared you.  He knocked you off your perch of optimism, hope and confidence.  Unforgiveable.  And yet, we do have to forgive the doctors.  Their emotional intelligence blunders more often than not are completely innocent - they just see things differently from us.  Take you, for example.  From your history and age, I would guess that this CML dx came out of the blue and that you had  probably never confronted anything medically superserious for yourself yet.  You were just bopping along in your young life, feeling pretty good, just living and definitely worrying about other things than your health.  So, first shock and awe, followed by possibly rough side effects which absolutely nobody cares about (felt fine BEFORE, now feel lousy and tired, etc - what's up with this?), followed by existential crisis, followed by education (and lurking here - yay, lurking!), followed (hopefully) by acceptance, perspective, calm, balance and wa-a-a-a-a-y down the line, a smidge of gratitude at your "luck".  

The docs are immune to all of this.  They see a million of you.  They see their job as moving you, like a chess piece, to the right place.  They feel secure in their knowledge (whether or not that is always warranted) but they don't see any reason to tell it to you - takes time, hard to explain to a "layperson".  They want to do right by you.  They are nonplussed when we complain or worry.  In their awful, horrifying world of cancer, this is a slam dunk.  They have moved so far beyond being scared for us that they simply can't understand how even bringing up a transplant is enough to ruin not only a patient's day, but week, month - in fact, possibly change their perspective on their life with CML forever.

My advice is to push this transplant worry away.  If you want, you can give yourself permission to worry just a little while before your next PCR (everybody does, no matter if they've been at this more than a decade), but until then, just go back to your happy place.  But I'd like to give you an assignment:  next time you see him, tell your hem-onc how what he said made you feel.  Explain it to him.  I hope he gives you an ear.  Do it for the next newbie.

I’m not sure that a transplant conversation it out of bounds. There’s nothing wrong with being prepared. My sister was tested for a HLA match upon my diagnosis, and she’s a match, which is handy information in the back pocket.

David.

Great advice Kat. 👏🏻

Thank you everyone for the overwhelming amount of positive responses. I definitely needed to hear some of this stuff.

I had time to sleep and re-assess the situation with a somewhat clearer mind this morning. I think what hit me hard was the fact that my hem-onc was very abrupt and abrasive during the entire meeting yesterday. I've seen him three times over the past twelve months, and I have always just accepted the fact that he was very straight forward -- which is what I prefer in a doctor.

Yesterday was a different story. He started off with the usual greetings and asking me how I was. I told him I was a little bit anxious because I caught a glimpse of my results from my family physician and I asked him if it we need to make any changes to my treatment. He responded with an attack on me, that I asked him about treatment changes before he got to ask me questions, and that the point of the meeting was for him to ask me questions vs me making demands on treatment changes. Anyway, there are two sides to every story, I did not thing I was being unreasonable by asking a question, but he took it the wrong way.

The entire session after that point was just cold, yes or no answers, and he basically walked me out of his office at the end with a requisition for the next MRD test, a referral to a transplant specialist, and an ultrasound appointment. 

Before anyone comes to my defense (or his!) -- I accepted that I do not have to like the doctor, he just has to be effective. I should appreciate his logic of geting me connected with a transplant specialist. It was just a bad timing of raising of my two kids (just had a second child six months ago) and starting work again. I thought I had my CML under control for the foreseeable future.

I never got the numbers for my BCR/ABL1 test that was done at the very beginning of this whole thing. Here in Canada, our public health care system does not really provide the numbers data on the tests unless you ask. My hem-onc doesn't really share the numbers either, he just analyzes and makes suggestions. I assume if I get another bone marrow test, that should include another FISH test?

I look forward to seeing my April results, I'll definitely post them up when I do get them.

Again, thank you for your words of encouragement!

 

 

Worse than I thought!  I understand your excuses for him - I did the same thing for two years - then, after therapy (!) I began to see that everyone deserves a doctor who can listen, respects you and your concerns, and has at least enough patience to answer questions.  You'll probably never find warm and fuzzy or fulsome sympathy, but to not share and go over your test results is - sorry - unconscionable.  I changed doctors and centers.  And when I ran into some of the same problems with the new guy, I politely stood my ground.  Many patients truly don't want to know anything - my mother-in-law is like that.  The doctor is god and her job is to nod her head and be sweet.  Doctors often don't know how to handle patients who ask questions.  Find one who does.  

I agree that this is good and necessary information to have should it be needed but just getting the information would always make me feel like that's where things are eventually headed. That's just me though I read too much into things. If I were hovering anywhere above 1.0 to 5.0 I would not think twice about getting all necessary information. HLA types etc.

This really was such a great post - I really appreciate your perspective and I'm very grateful you took the time to write it.  Thank you.

I absolutely agree with others who have questioned your doctors 'attitude'. This is not in my personal experience of being treated by expert CML haematologists over 20 years.

To talk of transplant as a next step at your stage of TKI therapy and with your positively good response is, in my opinion, at best inappropriate and it is not or should not be, in his remit to decide for you.

I agree that testing for a possible sibling HLA match as an insurance against future failure of TKi therapy would do no harm, however, your results do not show that your are failing TKI therapy by any means. It looks to me like you are responding very well.

In your place - at Kat has advised - I would take steps to change to another CML expert doctor, if that is possible for you to do... or at least get a second opinion.

I have had a transplant and it is not an easy option. If there had been a 2nd gen TKI available to me when I was showing some resistance to imatinib back in 2002 I would have opted for that. 

You should expect a better response to your concerns and certainly more respect from your doctor, or any doctor. 

As others have said, there are many patients who take longer to get to 0.1% slower than the 'guidelines/recommendations' reflect. It is not unusual and as David has said, your overall trend shows a reduction. 

Sandy

No doctor should ever recommend a transplant based on imatinib failure in 2021. There are many TKI's now available to try. In fact, several of these 2nd generation drugs are now prescribed first.

Imatinib failed for me. I could not even get below 50% FISH let alone PCR on imatinib. I also suffered tremendous myelosuppression on imatinib which prevented dose increases in order to try and get control of my CML. None of my doctors discussed transplant. Instead, I was moved to dasatnib low dose. And even dasatinib started off poorly - and still no transplant talk. I went a year with high positive CML and no trend downward. My doctor kept adjusting my treatment - (lowering dose in fact, not increasing it). Eventually, CML was brought under control through a 'pulse, on/off' approach. And I think my change in diet helped my immune system as well. Once CML trended down and I added Curcumin, my CML counts as measured by FISH and PCR plummeted to well below 0.1%.

Today I am drug free (just started TFR) and have been 'undetected' for CML for over 4 years.

My recommendation (and you have excellent advice in the posts above) is for you to switch drugs now rather than wait until 18 months - preferably to dasatnib (low dose only) or nilotinib. Either drug is likely to speed up your response and drive CML below 0.1% PCR. And changing drugs or rotating TKI's  can facilitate CML clone removal even blast crisis:

https://pubmed.ncbi.nlm.nih.gov/28416739/

Other drugs such as ponatinib and bosutinib are available as well to treat CML. If your doctor won't answer your questions - or address your suggestions in the spirit of collaboration, get a new doctor. The people on this forum together have more collective experience with CML both physically and emotionally than he does.

 

Thanks for the suggestions everyone! I saw this thread get revived, but I wanted to wait for my telephone appointment with the oncologist before I posted.

Re-reading my post from before -- it reminded me of how unsettling the attitude of my oncologist was back when he practically pushed me out of his office.

Fortunately, the transplant doctor that he referred was miles better in terms of being able to ask questions and get the straight answers in a professional manner. She assured me that a transplant is NOT something she would recommend given the situation I am in. My brother was tested and he is a half match.

I hope to not go down that avenue as the risk seems higher than TKIs at this point.

Now for some good news, I finally reached MMR (IS 0.069%), and it took just a tad over 2 years on Imatinib 400mg. On top of that, the oncologist was actually pleasant to deal with today, which is almost as shocking as reaching MMR.

Date IS Burden %
1/29/2019 134
4/29/2019 29
7/29/2019 3.3
10/21/2019 2.2
1/13/2020 0.73
4/16/2020 0.37
7/29/2020 0.18
10/27/2020 0.15
4/3/2021 0.069

Thanks again for all the responses!