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Sprycel - Lack of Response

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Hi All,

Feeling pretty discouraged and scared at the moment. I was diagnosed Feb. 2018 with PCR 97%. I was started on Sprycel 100 mg and PCR has been steadily dropping, but began dropping more slowly recently and has now started increasing at 15 months. My results are below:

PCR at diagnosis: 97%
3 month: 3.822%
6 month: 1.069%
9 month: 0.547%
12 month: 0.256%
15 month: 0.945% (now worried)

I read a lot about people switching to Sprycel due to lack of response, but very few that switch from Sprycel due to lack of response. It seems, most people switch from Sprycel due to side effects. I'm wondering if there is anyone out there that did not respond well to Sprycel, but switched to a new medication that worked successfully?

I found the same thing and was also very discouraged. My numbers are as follows on 100mg Sprycel:

64% at DX
23% 3 month
1.9% 6 month
0.81% 9 month
0.32% 12 month
0.58% 15 month
0.111% 16 month via bmb
1.2% 18 month.

We decided to switch to Nilotinib without mutation testing because it approaches the disease differently than Dasatinib and also does better if a handful of mutations are rearing their head (F317 I think is one). I just pray and will find out mid June how things are going. Just think that just because it is uncommon does not mean it is unmanageable. The great news is that you responded in the first place (others dont). Also some respond clinically but the blood counts drop to unsustainable levels which is not the case here. Keep your head up. Mutation testing is not a bad idea but we decided to give Tasigna a go for 3-4 months. I am much less worried than I was when test came in. There are many options for you. It just doesnt go perfect along the way. Take care.

Job,

Thank you for the response. That makes me feel a little better, but definitely still trying to come to terms with these results. My wife is also pregnant and due in June, so that is just adding to the stress and feeling of unknown. Can I ask whether you considered Bosutinib or Ponatinib and how you and your doctor decided on Nilotinib? Also, are you doing monthly testing while you try the new medication? Thank you again for the response.

Ian

I have 3 kids and is probably why I worry when I do worry. I did not consider the other two because the thought was to try a 3rd gen as a later option. I would add that I know someone who failed all but Ponatinib due to T315I mutation and that was over 7 years ago. He is pcr 0.02 that whole time. Others have had to go on and off medication for low blood counts and eventually found the right medication and dose.

The only reason I tried another med is because I went 0.111 to 1.2. In your case I probably wouldn't change anything just yet unless it climbed in two consecutive labs. I believe 0.5 is within error.

Sorry forgot to add I did a lab one month after starting Nilotinib but just to make sure nothing was climbing (WBC or basophil) and everything looked fine. Next test is 2.5 months out from last lab.

I know of someone. A friend of my daughter has CML, she’s 34, started Imatinib in Oct. 2015, went to Sprycel, went to Tasigna and is now in a stop trial. What are the odds of my daughters childhood friend and I ending up with CML, within three months of each other?

I texted her and confirmed that she failed Sprycel.

Prof Steve O'Brien talked about switching when PCR is drifting up in his talk at the patient day last September. His talk is here the bit about changing drugs due to PCR increasing is from about 14 minutes in. I'm lucky that I didn't need to worry about mutations; I responded (a little slowly, with a plateau for about 4 months) to imatinib, but got to MMR and have sustained), but having a read a few stories on here if you've switched to nilotinib or dasatinib and are not making progress mutation testing is a likely next step.

Hope this is useful.

hi, buddy! first of all, you need a retest. You should not change your treatment based on a single pcr because it's a very sensitive test and a lot of variations can happen (i'm 5 years and 4 months into treatment and i mmr4 - 4.5 with a lot of variations). I know a patient who went for MMR4 to 1% and than had a retest and she was mmr4 again (i.e.: the 1% was a lab mistake). You also should look for interactions (drugs and food). Good Luck!

Thank you to those that responded. It has made me feel much better. I feel like I have a general plan of action now when meeting the oncologist: First retest for PCR and if the trend continues up perform a mutation test. If the trend continues up it helps a lot to know there are others out there that did not respond to Sprycel, but we’re able to respond to other medications.

Thought I'd provide an update on my recent retest. 

PCR at diagnosis: 97%

3 month: 3.822%
6 month: 1.069%
9 month: 0.547%
12 month: 0.256%
15 month: 0.945% (terrifying)

16 month: 0.315% 

My take away from all this is: Still not a great response, but it illustrates what many have said in the past. Tests have a large level of inaccuracy (1/2 log as I understand) and one blip up (however terrifying) shouldn't be solely relied upon to make a decision. I still wonder if my response with 100 mg of Sprycel is good enough to continue with the same treatment, but for the moment I'm celebrating the fact I didn't have two consecutive increases. I wish I could go back in time and tell myself not to stress constantly and lose sleep over these results.

Good news. Over the 12 years I've been on the site I've seen quite a few sets of results with this sort of pattern. The majority stay around 0.25% for a few months and then suddenly BOOM - MMR. I hope you find in time you are a member of that majority.

Thought I'd provide an update on my 18 month test and hopefully get your thoughts on next steps:

PCR at diagnosis: 97%
3 month: 3.822%
6 month: 1.069%
9 month: 0.547%
12 month: 0.256%
15 month: 0.945%
16 month: 0.315%
18 month: 1.06%

Unfortunately, it has increased again and I assume indicates Sprycel may not be the best medication for me. I meet with my oncologist soon, who is not a CML expert. I plan to request a mutation test and a change to Tasigna or Bosulif. Do you all think this is the right course or am I missing something?

Thank you all for your great insights

 

I also could not reach MMR with Sprycel and changed to Tasigna. I did the change without mutation testing but PCR dropped from 1.2 to 0.36 after first test on Tasigna. Obviously hoping for better this next one in September but it is back going in the right direction. I provided an update which I think is called Sprycel to Tasigna or something like that. Mutation testing cant hurt but just switching seems to be working for me as it approaches the disease a little different thank Sprycel does. Keep us posted for sure as there is not a lot of people who dasatinib is not good for but that doesnt mean it is not treatable.

BTW my previous posts are under Job Guerra which I can no longer log in as but ColoradoGuy is my new alias ;-)

Thanks for the information ColoradoGuy/Job. I appreciate hearing from someone that has experienced a similar response. I am hoping to also try Tasigna and hopefully have a good response too. I will keep you updated. 

My oncologist just notified me that she would like to wait for 6 weeks and retest. I am nervous about this approach and would prefer changing medications now. Am I being to rash based on my recent results?

Maybe they are looking at it as your first time losing CCyR and no two results climbed consecutively. I had to wait for Tasigna approval for about a month so IMHO I dont think it is crazy to retest. You barely lost CCyR and 0.5 is within test error.

My onc says it is not something that can run away from you suddenly. You will know in 6 weeks but perhaps mutation testing to know what to switch to in six weeks in case it climbs again?

Hope your numbers drop next time around and if not there are many options. Try not to stress and I know it is easier said than done.

Thought I'd provide an update to my most recent lab testing. We attempted to perform a mutation test, but the PCR was below 1% now so they were not able to perform the test. Update is:

PCR at diagnosis: 97%
3 month: 3.822%
6 month: 1.069%
9 month: 0.547%
12 month: 0.256%
15 month: 0.945%
16 month: 0.315%
18 month: 1.06%

19 month: 0.28%

I am surprised at the magnitude of these bounces and I'm not sure these bounces could be called a plateau. My oncologist noted that the 19 month test was performed by a different lab than previous and she plans to use this lab going forward. She wishes to keep me on Sprycel and perform another test in 6 weeks. I am unsure whether sticking with Sprycel is the right approach, so I am trying to get a second opinion from another oncologist. Unfortunately getting a second opinion takes longer than I anticipated. I've been feeling pretty anxious about this. Does anyone have thoughts on whether I should continue to stick with Sprycel (and my current oncologist) or try to switch drugs immediately and look for another oncologist? Thank you for your thoughts.

In many cases when response is quick in the beginning but then plateau's at a low, but significant level, there is presence of another CML clone.

Do you know what your CML clones are? (usually p210, p190, etc.). One or more clones get wiped out pretty quick leaving the other clone to "fester" sort of speak and they sometimes expand to fill the void. As you are seeing, the lesser clone is under some control and is bouncing around at a low level. It is possible these secondary clones die out (often in fact) or can initiate new disease and require a different drug approach. What is your blast cell percentage? if zero or only a few percent - you have time to sort this out. Your overall low PCR is encouraging.

While you are waiting on results - augment your therapy with immune boosting nutrition to help your TKI do its job:

1. verify your vitamin D status is above 50 ng/ml (simple blood test). If not, supplement with vitamin D3 to get your D level up to around 70 ng/ml. Vitamin D activates your immune system. Low vitamin D is like leaving the T-cell army in the barracks while invaders are attacking. Also - vitamin D buys you time while you sort out drugs.

2. Add quercetin to your diet (food and/or supplement).

3. Add Curcumin to your diet (at least 4 grams per day) C3 w/pepper preferred.

4. Add selenium to your diet (2-4 brazil nuts per day OR 200mcg supplement - not both at the same time - alternate).

Take the fight to CML with all you have - not just sprycel.

One final controversial point:

There is evidence that less sprycel can be MORE effective than your current dose of 100 mg. I know that sounds counter-intuitive, but a dose of 50 mg may actually give you a better response. This is because sprycel is immunosuppresant. In addition to sprycel attacking CML, it also suppresses your normal immune system from attacking CML. Research is showing that there is a median dose which maximizes both CML response to the drug and immune system response to CML. Higher sprycel dose leads to no change in TKI response, but lowers immune response leading to overall less response. Only when my dose was dropped to 20 mg, did my PCR plummet. Many people are "undetected" while taking only 20 mg. I am "undetected". These are relatively new research results and do not apply to everyone. Finding the right dose (especially with sprycel) is key.

Also - switching to Nilotinib could very well wipe out the residual clone. Multi-TKI strategies are an effective plan as well. Your doctor should not hesitate to swich you so you hit CML from many sides.

When dealing with CML - an all of the above applies. You will get there. Just stay vigilant and keep learning.

Hi Scuba. I believe my clones have been detected for P210. I think after the first test the P190 was no longer tested for. It was also noted in my most recent test that I had primarily b2a2 (approximately 0.28%) and a smaller portion of b3a2 (something like 0.05%) or maybe it was vice a versa. I was just shown this on a piece of paper very quickly during my last meeting and don't quite understand it's meaning. As far as blasts are concerned, the last test that checked blasts was in April 2019 and I had 0% blasts. Should I be testing for this more frequently? I have been taking Vitamin D, and tested for it once. It was 29 ng/mL. Which I understand to be on the low side, but not incredibly low. I will look into the other suggestions. Thank you.

Thank you for the update.  It is encouraging that it trended down as opposed to the opposite direction.  What Scuba mentions regarding residual clones makes a lot of sense and perhaps giving Nilotinib a try will push you towards those elusive lower numbers.

I will say that I miss taking one pill a day and not worrying about fasting.  I am encouraged with my first Nilotinib result and will keep you posted on my next one (mid-September).  

My oncologist mentioned that he has patients at around 0.2 for years without any changes in health or survival (maybe they tried a couple and do not want to go to Ponatinib or SCT conversation).  I think being below 1.0 and closer to 0.1 is considered a 'safe' zone and provides the same overall survival as MMR.  The bad news is that it does not look so good for TFR which would also be a great thing to reach.  

Hang in there and who knows maybe your next test or a switch will be just what you need to get to those lower values and keep them trending down.  

Thanks ColoradoGuy. I am very interested in your progress as we seem to have a very similar experience. I asked my oncologist about switching to Nilotinib and she was against it at this time. I really would like to switch and that's why I'm in the process of getting a second opinion. I'm wondering if there is difficulty in switching due to insurance? I'm also in the states (California).

I take 5,000  IU's vitamin D3 per day during summer and 15,000 IU's over two days in winter. Any level below 50 ng/ml is not effective in cancer prevention. So consider supplementing. My supplement program keeps me around 70 ng/ml and above 50 towards end of winter. It takes months for vitamin D to go up or down.

There should be no difficulty in switching due to insurance as anybody that covers Sprycel will have no issues covering Tasigna.  It is a matter of paperwork and pre-authorizations for the new drug.  That does take about 2 weeks (in my case took a month).  I was lucky that I had squirreled away some Sprycel from a time when my insurance was switched and had two weeks extra which helped me keep taking it while the approvals happened.  I had to call my nurse/pharmacy/insurance company at least three to four times each to get everything squared away.

So really my numbers may have climbed from 1.2 (when I switched) while I did this dance.  Nilotinib seems to be working with no side effects at all.  If you really want to change ultimately it is your decision and should be handled as such.  I will say that they probably see a lot of people that have a terrible time with side effects so when they see a case with minimal to no side effects they are reluctant to change.  

BTW I'm taking 4000IU Vitamin D and Curcumin tablets but after reading Scuba's post may up that to 5000IU.  Take care and I will keep this thread up to date.

 

Guy in Colorado - Best to get a vitamin D test so you have a baseline. You'll need more or less daily vitamin D depending on where you are starting.

I had it checked at the end of February and it was 23ng/ml which showed to be on the low end and not adequate.  I have not checked it since then but have only recently (three weeks) started taking the 4000IU.  I was previously only taking 2000IU.  Thanks for the info.

Hi Scuba and others. I just want to follow-up on my question regarding the frequency of tests for blast %. I got my last one about 5 months ago with 0%. Do you know if most people get this tested more frequently? I've done CBC's every three months in the past, but the blast measurement was uncommon and I think was only measured 5 months ago and at diagnosis. I'm just wondering if I should be pushing for this test to be done more often given my situation? 

I asked this question of my onc once.  His reply was that IF there are blasts, they will be recorded on your CBC.  The fact that nothing is mentioned means there are no blasts detected.

See Kat's response.

Blasts % is reported with every CBC and if zero blasts, often not reported at all.

Blast cells are very fast differentiating cells. They do not stay long as blast cells .... sort of like muons.

If Blast cells are measured in significant amounts, something is wrong - hence importance in leukemia.

Most people have zero to a few percent. Zero doesn't mean none - we all have lots of blast cells created, they just don't stick around.

In CML, blast cells do not differentiate and instead accumulate. This is the part of the disease that kills. When blast cells accumulate in sufficient quantity because they are not differentiating - it's hard to undo - sort of like a roach infestation. Need to burn the house down otherwise known as a stem cell transplant.

Interestingly. Vitamin D is necessary for blast cells to differentiate including leukemic blast cells.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2820234/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5303117/

In fact, vitamin D receptors are on blast cells including leukemic blast cells in large number. Without vitamin D, differentiation is slowed down or stalled.

In my own case, I always had blast cells. At diagnosis, my blast cell count was very high bordering on accelerated phase. My vitamin D status was also very low. Even during treatment, my blast cell count was never normal. ONCE I started my vitamin D protocol raising vitamin D from 17 ng/ml to around 70 ng/ml where it is today, my blast cell count fell to zero. It has been zero ever since.

More than any other indicator - blast cell percentage informs whether you have time to experiment with drug dose an other protocols. As long as blast percentage is zero or a few percent - ideally zero, one can experiment with dose and other trials because CML is a very slow disease when in chronic phase.

(I wonder if I ever would have developed CML in the first place if I had known about vitamin D's importance to the immune system and cell differentiation and kept my vitamin D level where it is today. I know of no one who had high normal vitamin D level at diagnosis. It seems low vitamin D is a requirement to trigger the disease among other things going wrong. It's not a cure, but could have, perhaps, been a preventive.)

Yes, Scuba, I think there is a connection.  My Vitamin D was super low at diagnosis.  Love your roach/burn the house down analogy - makes perfect sense.

Well I have an update on my 2nd lab on Tasigna (6 month) and 25th month overall.

0.36
Down to 0.34

So not really down at all. Just steady and no increase. I know MMR is the goal and of course TFR but Im wondering if anybody has been in CCyR without MMR for a few years. I may up 600mg Tasigna to 800mg and see what happens and probably mutation testing is in order. I have tolerated Tasigna very well and don't really want to change if I don't have to.

So should I be as calm as I am or is more serious discussions in order?

Hi ColoradoGuy, I ended up visiting Dr. Shah at UCSF (a CML specialist) over my results since they have been similar to yours fluctuating under 1% but above 0.1%. He told me that he was not overly concerned with my trend so far. He said a lot of younger men tend to catch CML a little later because they tend not to go to the hospital as early or frequently. He said because it is caught later, often times it takes longer to get to MMR and possibly may never get to undetected. He noted that it is more important to remain in CCyR for a couple years. If you remain in CCyR for a couple years your overall survival likelihood is very good/comparable to MMR. 

Just my two-cents, but after he told me this I felt a lot better. I just drew blood for my 21 month test and should find out the results in the next couple weeks. I'll keep you updated as we seem to be moving along a similar path. My thoughts are with you, and I'm hoping you remain under 1%.  

That's funny I just left my onc appointment and he said something similar regarding younger patients. He was not concerned right now and in fact advised against raising dosage. He did feel hanging out above 1.0-10 is a different animal and would be going about it differently in that case. Praying for numbers going down in the near future (yours as well).

Just an update on my response to Sprycel. Just had my 21 month test results and got the following:

PCR at diagnosis: 97%
3 month: 3.822%
6 month: 1.069%
9 month: 0.547%
12 month: 0.256%
15 month: 0.945%
16 month: 0.315%
18 month: 1.06%

19 month: 0.28%

21 month: 0.28%

My oncologist does not seem too worried even though I still have not reached MMR. She reiterated to me that if I stay in this zone without an increase in PCR my survival likelihood is the same as reaching MMR. She noted it's possible I may never get low numbers and I'll just hover around here. I'd obviously like to get to lower numbers, but I also feel fortunate to be where I am and have this medication. Is this trend concerning to anyone? Should I be more worried? 

Hey bud, I've been following your posts from the shadows and figured I'd reach out. I'm right around your age and was into treatment about your same length when my results were mirroring yours. I was constantly bouncing on pcr's up and. down, up and down. It was quite taxing mentally. I was between like .3 and .9 for probably a year or 1.5. I missed mmr at 18 and then 24 mo. but finally hit it with a random drop at about 25 or 26 mo. Luckily I have maintained it and further decreased for about the last 2.5 yrs. but still experience the fluctuations.

It's common for us youngsters. I would try to avoid stressing. You are at a real .30 it would seem with the consecutive tests, and overall that's really good in the big picture. Take care.

Thanks for the update as I am following your trends (similar to mine as you know).  It looks like your 18month may have been a lab error (maybe as a big bounce at 15 month as well).  That being said it looks like you have been in CCyR for 15 months.  That is good and staying so for 24 months would be ideal for probability of remaining there and even dropping in the future.

My oncologist feels that lower CCyR numbers are no reason to change and said it's best to let it reveal itself over the next few months (slow trend up or down).  Of course I'm praying that I see a sudden drop after plateau which I have read of many such cases.  

Remember that the definitions/parameters have changed over time and earlier people would not have given our numbers a second thought and reached good results years later.  

I think they pop out to us because of the natural lure of ND and TFR (functional cure).  I will update this thread in a couple months when I get my next results.

Thank you for posting your positive results for those of us who are around the same age and seeing very similar trends.  Very encouraging.

I was just looking at my own results, it took me 19 months to achieve MMR some years back. I wasn't the fastest responder.

I got my most recent result today (on 20mg of Sprycel, after an 18 month dose reduction plan) and it was MR5 - which is a first for me. It's been hovering around MR4-4.5 for a while before.

David.

Busaboy, David, and ColoradoGuy. Thanks for sharing your experiences. I feel much less anxious when I hear about similar trends. Sometimes I think it would be better not to know the milestones set out in the guidelines.   

My history mirrors David's, except it took me 22 months to reach MMR way back when.  But I'm in the same place now, on 20 mg Sprycel.  (The 22 months were on Gleevec, so perhaps for me, Gleevec was turtle food and if I'd been on Sprycel from the get-go I might have been faster.  Who knows.)