TKI and therapy

Welcome to the forum. I believe no one chose to be here, but it is great company :)

CML is conservative and slowly progressing... until it isn't. When (now, luckily, IF) it gets to the blastic phase, it becomes as aggressive as any acute leukemia. The point is we do not know exactly when it starts to progress; for this reason it is a safe policy to have as lower a PCR value as one can. 

What is more, treatment free remissions protocols are based on the assumption that you have been on PCRU or a similar level (MR 4, under 0.01) for at least two years. You do not know whether you will be able to stop a TKI sooner or later; yet I can definitely tell that unless you stay under MR 4.0 for two years most doctors will be against you trying TKI interruption.

More generally, CML is a strange beast. It is cancer, a leukemia, that is a very bad cancer. Yet the state of the treatment is so good that you can forget you have a serious illness. Nowadays, luckily, most patients have little idea of what CML can do, if left untreated. A strange beast indeed, but a vicious one nonetheless; luckily we manage to keep it dormant, but we should not forget what we're dealing with.

About a "start & stop" approach to treatment, I believe there are two classes of problems there.

1) a number of studies suggests that a stable lower dose works best than an intermittent higher one; I read that here or in the lls forum some months ago.

2) Starting a TKI after stopping it is not as easy as it seems. I had a 3 weeks break from Sprycel. I felt wonderful during the break. Yet, resuming was kind of hard. I got the headaches, the skin rashes and all the side effects that I had when I started Sprycel for the first time. The intensity of side effects was lower, and I felt better because this time I hadn't any of the symptoms of leukemia per se; yet, coming from a state of full health (no CML symptoms and no TKI) it still was troublesome. I was not monitored daily, but it makes sense to suppose that my blood counts also took a small dive. When you are on TKI for a while your body gets used to it; as soon as you stop it forgets about it, and then starting again is not easy. Seven months have elapsed since I restarted Sprycel, and I feel great again, much better than when first resuming.

I am sure someone with more experience and a better grasp of CML physiology will give you a more precise answer :)

Cheers!

Davide

Well, first of all let me assure you TKI do not create mutations :) A mutation might naturally occur if CML is left alone or not tackled in the appropriate way. It is an instance of natural selection: TKI kills the "standard" CML cells, so the mutated ones become prevalent. Also, CML progressing is in itself a form of mutation: this is what cancers do, the more they progress, the more variants they create, and that is why they are so difficult to treat. 

Many CML experts (talking about doctors here, including mine) believe that mutations might arise when the dosage of a TKI is not high enough. Others believe that this is irrelevant and mutations would have developed anyway. The first group of doctors is usually more resistant to the suggestion of reducing dosage. The science is not 100% set on this, so both opinions have some foundation. However no one believes that TKI is directly responsible for the arising of mutations; you should not worry about that; as far as CML is concerned TKIs are good for you. They work well, and they are more targeted than interferon; back in the days interferon did not work for everyone, while nowadays curability in the chronic phase with TKI is very very very high, much higher than it was with interferon. Interferon might give a boost to TKI, but I believe it is an experimental approach, reserved for complicated cases; it is a nasty drug, a TKI regime is much milder. 

As a consequence, I would not worry about interferon and the like; the standard protocol of "just one TKI" works very well, as your PCR exam goes to show. You take your TKI, at the prescribed dosage, and it will do its job. Your job (and mine as well) is eating healthy, exercising and enjoying life; this will definitely help your recovery. When you get to a very low PCR value (MR4), then maybe start talking about dose reduction.

Also, I think about this often, who knows what will happen in the CML world in 3 or 4 years? New meds are undergoing testing, studies on dose reduction and treatment free remission are progressing... We have a front row seat :)

I really would like to believe you like that kinase inhibitors do not cause mutations. I would be less hesitant and I would continue my treatment. Unfortunately, Thomas tells me, so I have the right to be unfaithful! 😊 Dear David, I quote the following link, which refers to the topic: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4309587/ In short, all of us who get TKIs have to wait for mutations of the gene. Another issue that exists with TKIs is that we have an increased rate of secondary cancer growth. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4895174/ TKIs are not a panacea, they also have drugs as their side effects, which are important. The issue is what everybody wants us to die ... from the cml or the side effects of the drugs. Sorry I speak hard. TKIs are sure to increase our lifetime. We need to use this forum for the benefit of all. We all have to work together to find the ideal treatment ... and always with the help of God!

I dreamed I fell into the dark ocean.
Someone threw me a raft.
I reject the raft because
I might die after I’m saved.