Hi, I've had CML for over sixteen years and its been controlled well enough with glivec with just a few singular spikes through the years. My last result was 0.28 and my consultant stated that I would have to change drugs if it increased anymore. My normal bloods were fine at this time.
I just wondered how its determined whether you've built up a resistance to the drug or you've gone into the accelerated phase.
Thanks
Graham
Hi Graham,
Resistance can often be caused by a mutation of BCR-Abl, meaning imatinib is less effective against it thus seeing a spike in your numbers. Since you have gone above 0.1%, your doctor is right to do something about this. Guidelines (ELN) would steer towards changing TKI if you lost MMR (0.1%) and it was confirmed by two tests.
The ultimate test for a mutation, as I understand it, would be done via cytogenetics - i.e. a bone marrow test. However, this is often not done prior to switching drug. The reason is that the second generation drugs are usually effective against mutations other than T315i, which is rare. So, there's a certain logic just to change drug rather than go through a bone marrow test to look at what particular mutation you might have only to prescribe the same 2nd generation TKI you were going to, anyway.
In the mast majority of cases, the 2nd generation TKI will bring you back into MMR.
On the point of accelerated phase, this is usually defined as a certain level of blast cells in your blood. With a PCR of 0.28, you won't be in that position.
David.
Hi, graham. First of all, i'm sorry about this situation. second: we need more information. how was your last 3 results (PCR)? are you taking your meds every day (adherence is the key!)? I don't think you're in accelerated phase, but it depends, mostly, if you have and increased blasts in the blood or if you have some clonal evolution in the marrow (another chromosomal translocation) If i were you, i would have a retest. Good luck.
Hi Lucas,
My previous PCR was 0.1 and the ones before that were below 0.1 as per normal.
My last spike was about 4 years ago and was a singular peak. The consultant is
doing another test, so there will be a three month gap from the last.
My concern is that it appears an increase in dose is not a consideration and I
do not wish to change to Tasigna because of the side effects. Rather I would
accept whatever time Imatinib gives me.
Graham
Graham - Don't give up! Why not switch to Sprycel? I call it the "kitchen sink TKI" because it covers more kinases than any other TKI - it's potent and short-lived, and smaller doses (like 50 mg) pack plenty of wallop. The side effect profile is actually really good, if you can avoid the pleural effusions (2 out of 3 people do avoid them) and those occur at higher doses, usually. I went from Gleevec directly to Sprycel and noticed absolutely nothing except relief from baggy eyes, malaise, and nausea. I remember when there was a lot of excitement about Tasigna, but the years have not been particularly kind to its reputation. More and more people DON'T like it. If I were in your shoes, I would take hold of my courage and try Sprycel. Get that PCR back in line and re-evaluate - don't give up! Arm-chair psychology here: I sense that you are colossally and understandably angry, disappointed, resentful and scared because your Gleevec has failed and your body has betrayed you. This wasn't the way this was supposed to go, right? Please go ahead and be angry, but please don't punish YOURSELF by refusing to move to another TKI.
chin up, buddy! you should check for some interaction: food or drug (a lot of things can interact with tkis) and have a retest soon (and a mutation analysis), If you were in MMR3, maybe it's just a normal variation. About a tki change: i wasn't doing fine on glivec - very slow - and doin' great on tasigna (always under MMR4) and with very few side effects. Good luck!
