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Appointment with Dr. Druker; Considering changing TKI

Hi,
I haven't been her in a long long time. I'm in the U.S. but found this to be the best support resource for me. My son was dx'd with CML in 2008 at the age of 10. He's now about to turn 15. He's been taking Gleevec 400mg since dx. He's at MMR & his IRIS score is .00031.

My son has sort of levelled off as his numbers aren't going down any further. My father (who attends the International Hematology Conferences every year) is pushing for a TKI switch to Nilotinib. My father's view is that if my son reaches CMR and holds it for 2 years, then he can stop all TKIs. His view is that Nilotinib brings a deeper response - which is better even if my son continues on maintenance therapy.

My son and I will be seeing Dr. Brian Druker in a few weeks and I wanted to discuss the possibility of switching TKIs.

Can anyone share any thoughts on switching TKIs? I've read about rash with Nilotinib. Right now, my son's only side effect is terrible fatigue. He may have a resorption issue too because he fx'd his spine recently and last year, he broke his femur. I'm not certain about that, however.

Any thoughts would be so greatly appreciated! Thanks so much.

Tracey

Hey Tracey.

If i read you correctly, your sons BCR-ABL PCR results are 0.00031 International Scale?

If so, then he is in fact CMR already.

MMR is at 0.1%(3 log reduction), and CMR is 0.005%(4.5 log reduction).

If you are not using the International Scale, then the numbers are a bit different.

If you are seeing Dr Druker you are in good hands, but it seems your son is doing very, very well on the current TKI if Internation Scale is being used.

Please keep us updated.

Hi Tracey, I understand how the imatinib side effect of fatigue must be affecting Ben.. especially as he was so young at diagnosis. Regarding the other issue you mention with his spine and a broken bone, it might well be that imatinib has effected his ability to absorb enough minerals -calcium/magnesium levels are crucial here. It might be worth having his magnesium checked as it is possible to supplement or use magnesium salts to get the levels back to normal.

I am sure you are doing the right thing in seeing Brian Druker- I can think of no one more qualified to advise you both.

I am not sure how nilotinib might suit Ben as an alternative- as the required fasting might be hard for him to maintain. Is dasatinib an option? this TKi does not require fasting and can be take with or without food.
Given his PCR (IS) result shows he has very low levels of bcr/abl at 0.00031%
(0.0032% Bcr/Abl% = MR 4.5 on International Scale) it might be that he would be able to enter a stopping trials if he has held that low level for over 2 years?

So there are more options- particularly for stopping studies- coming on stream. I am sure Brian Druker will discuss all those that are available in the US.

Please keep us updated here. Best of luck,
Sandy

*Low levels of Magnesium is indicated in joint pain/muscle cramps and is easy to supplement. He could try magnesium oil or magnesium salts as a daily bath soak.

Thanks for your thoughts.

I didn't know that Ben's numbers are considered CMR. I always thought he was MMR. (he is .00031 on the international scale - I used the wrong term in my post.)

I'd love to get him into a study but he's only 15 now and is not permitted to participate. My local oncologist said that she believes his success is due to being very very compliant.

Dasatinib may be an option for a change. The fatigue is really devastating for him. He missed most of the school day today! I didn't realize that Nilotinib was so exact. Now, he takes Gleevec 2x per day (he uses four 100mg tabs) so I thought the switch wouldn't be so hard.

IS THERE ANY TX/SUPPLEMENT THAT YOU KNOW OF TO IMPROVE HIS BONE STRENGTH? I'll get his mineral levels tested next week. He had a bone density test after he fx'd his femur and that was normal. That was only an xray type test though.

Thanks again for your thoughts and help. You guys are the very best resource I know!

Have a wonderful day.
Tracey

Dear Tracey,
Just a note of clarification on what is CMR and what is MMR. Chris Warden and I, have been working on a booklet to help patients understand their PCR results. We are still at the proofing stage and hope to have the go ahead to publish very soon. However, I think the following excerpt from our booklet might help this discussion.

"LEVELS OF MOLECULAR RESPONSE:
Up until recently (2012) the ‘holy grail’ of CML patients treated with TKi therapy was to achieve CMR (Complete Molecular Response). However, it is now considered to be misleading to use the word ‘complete’ because this might be generally misinterpreted to mean there is an eradication of the disease, as in 'cure'.
Currently the majority of patients need to continue with their daily therapy even after reaching Bcr/Abl levels that equate to a CMR. There was a recent consensus agreed between international CML experts and clinical groups to stop using the term CMR and replace this with MR+ log number, as in the following definition:

Bcr/Abl percentage or log reduction on the International Scale:

0.1% Bcr/Abl = MR 3 (3 log reduction from 100% - IRIS baseline)
0.01% Bcr/Abl = MR 4
0.0032% Bcr/Abl = MR 4.5
0.001% Bcr/Abl = MR 5

I am not sure if you have given the correct number of zeros.... you have 3 after the decimal point. But if that is correct then Ben's result of 0.00031% is below MR5/0.001%

Hope this helps,
Sandy

Hello Sandy.

Im just wondering why MR 4.5 is now 0.0032% instead of 0.005%, as ive read other places (and here) that it is 0.005%.

I am currently at around MR 4 (0.01%) and i though i just had to get to 0.005% to be CMR, or so i thought.

Ill be sure to check out your booklet :)

Thanks, Teddy

Hi Teddy, not sure where 0.005% was cited as a 4.5log reduction. I have only ever seen this cited as 0.0032%, but maybe if it was on this forum it was a mistake or a typo! There are presentations that I have seen recently that use this definition for MR4.5 but we are checking our booklet with CML clinicians so that we don't make a mistake.

Your current status is pretty good at 0.01% = MR4. I'm hoping you see another zero next time.

Sandy

Thank you for replying. I will use the contact form on the "Contact Us" page to send you a message so i dont hijack this thread. Oh, and im hoping for another zero as well :)

Teddy.

The correct figure for a 4.5 log reduction is 0.0032% because it is a log scale. In a log scale, half way between 1 and 10 is the square root of 10 which is about 3.2 so the extra 0.5 log reduction reduces the count from 0.01% to 0.0032% rather than 0.005%. I could have given a more elegant mathematical explanation 40 years ago when I was studying at university!

Thanks so much for your help! I'm always so grateful to everyone here for your thoughtful responses. Have a great day!
Tracey

Strontium ranelate (sold as Protelos by Servier) increases bone formation and reduces bone resorption. It is used to combat osteoporosis and has shown significant improvements in breakage rates.

My wife is on it after she could not tolerate bisphosphonates (which shuts down both formation and resorption) and has no noticeable side effects.

Drawbacks:
The dosing regime requires no calcium containing food for two hours before or after taking powder - inconvenient.
Stontium screws up bone density tests like DEXA. There are algorithms to compensate, but there are still difficulties in bone density measurement.

No idea whether it is any help for your case, but it might be worth asking the question.

John