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Need advice on pcr results

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Hi guys, I was diagnosed February of 2018 and I’ve been on sprycel 100mg till now. My doctor is suggesting to higher my dosage to 140 

Dignaosed February 2018 100mg sprycel 

May 2018 Pcr results 0.5 

October 2018 results 0.05 

May 2019 results 0.08 

after the last result my doctor is suggesting to higher my dosage to 140mg I have no idea if that’s a good idea. His explanation was that he wants to get it 0.00 as fast as possible. But I’m trying to lower my dosage not increase it. With my pcr being so low i don’t know if that’s a good idea. Need advice thanks! 

You're in MMR, which is a good place to be. 140mg of dasatinib is a lot and is known to lead to greater side effects.

You're only been diagnosed barely over a year, so being in MMR is good and your current dose (and perhaps lower, in time) seems appropriate. 0.000% shouldn't be the goal, certainly not at 15 months of treatment.

David.

Thanks david, i was worried about the side effects as well. Do you know if you have to be on undetectable level to live out a full life. Can you tell me how long you were until you went undetectable for your pcr test and how long youve have cml for? Im worried that once i go to 140mg might be too strong and i cant go back down to 100mg bc my body isn't fighting the leukemia cells like they were, if that makes sense.

Trevor,

As crazy as it sounds - you are likely to have a faster result downward by LOWERING your dose from 100 mg currently to 70 mg or even 50 mg. I'll explain.

Dasatinib (sprycel)  is a "threshold" drug. Its half life in the blood is only 5 hours, so it works right away or not at all. It also impacts our normal cells during that same time (not just side effects) in that it causes suppression of our immune system. Adding more sprycel in the mistaken belief that more is better and leads to deeper response has been proven false (for dasatinib). The key is to find the correct dose for you. If 100 mg is getting you to 0.05-.08 (which, by the way is statistically zero difference - you simply have plateaued at that level), then lowering your dose to 70 or even 50 mg could very well take the strait jacket off your immune system while also attacking CML. It's not the dose, it's the threshold. That threshold dose is different for everyone. The new starting dose for sprycel is emerging to be 50 mg ! because of the success rate and the much lower side effects (pleural effusion).

https://www.ncbi.nlm.nih.gov/pubmed/29723397

I take only 20 mg sprycel and I am "undetected". It wasn't until my doctor lowered my dose that my PCR plummeted. You want your drug and your immune system to fight CML. Too much drug hampers your immune system, so the idea is to find the sweet spot where both drug and immune system is fighting CML. Some patients need more drug to cross over their threshold. For them 140 mg gives the same result as 70 does for someone else. We're all different.

Given your current PCR (and I assume you have few blast cells), you can experiment with lower dose for one cycle (6 - 12 weeks) and see how it works. You can always increase your dose. Or just stay where you are and it's quite likely you will break through your plateau and resume your drop.

Show your doctor the paper above - chances are he has not read it. Ask him how many patients he has and at what dose. Inform him you know of patients taking only 20 mg and have had incredible response. In fact, you should tell him you know patients who only after LOWERING their dose did their response increase. Most patients had to lower their dose due to side effects and then it was observed that their response improved. That's how they found out this inverse correlation. It's not true for everyone - so it is an experiment to try.

All the best.

 

I've never been undetectable. It's not necessarily a realistic goal. As PCR technology improves, lower and lower amounts of residual disease may be found and those who were "undetectable" may no longer be, even though nothing has changed for them. 

Once you are in MMR, and maintain that, all the evidence and experience shows that you'll lead a normal lifespan. 

David

David - in fact patients achieving CCyR, complete cytogenetic remission (PCR ~ 1.0 %) can expect a normal lifespan.

MMR is truly a very deep response at the molecular level.

I agree with you, however, as PCR technololgy sensitivity improves, we may very well find everyone in the general population has bcr-abl!

It's just impossible to imagine that all cells can avoid the 9;22 translocation. The abl portion and bcr are perfectly aligned next to each other at mitosis. It's any wonder so few contract CML. DNA is amazing stuff.

It is estimated that those who achieve "undetected" status are probably circulating over a million CML cells. In comparison, a human body is typically circulating 30 trillion red blood cells. A million is a small number indeed. Easy to hide away among the trillions.

regarding PCR results 

the Best bit of guidance I was given by my Hematologist is that the PCR blood test is like playing darts you either get bulls eye or you miss the board altogether. Plus subject to the sample size take results can vary. The most important thing you can do is to trust your team and let them monitor your results and well being, they will adjust your treatment accordingly if deemed necessary.