21 replies to this topic

[mscl]

5+ years since Dx. Late in year 3, developed pleural effusion, cleared that up and reduced to 70 mg Sprycel. PE came back, so reduced to 50 mg. Late in year 4, developed a horrible, horrible skin rash, cleared that up, so reduced to 20 mg. I have been on 20 mg since January. Doctor appointment today and still undetectable, so low dosage has been successful so far for me.

[M.A.]

This is wonderful news mscl! So glad to hear your rash cleared up and that 20mg is keeping you undetectable. Thanks for sharing your story.

 

I just got my one year BCR ABL report and I am massively, massively relieved that the 50mg I'm on seems to be working.

 

My haematologist said at my last appointment that he would prefer me to be on a higher dose but I start a new job on Monday and have been freaking out about how I could manage it if I had to increase my dose again. Phew!!!!

[scuba]

https://www.ncbi.nlm...pubmed/21084830

 

http://www.clinical-...0014-9/abstract

 

It has been known for some time that normal dose Sprycel (100 mg) is higher risk for pleural effusion and other serious side effects. It has also been known since 2010 that low dose Sprycel can be as effective as the higher dose in achieving molecular remission.

 

My oncologist never started me on 100 mg sprycel. He told me it's too high for most patients and that a lower dose - even a much lower dose can be as effective. He described it to me this way - Sprycel is a threshold drug. CML response to it is not dose dependent.  Once a minimum concentration is reached it's effect (if it is going to work at all) is dramatic. More is not better. More does not deepen response. More is dangerous. He preferred to start me on low dose and work up if necessary. Turns out, 20mg Sprycel was quite effective (PCR < 0.01%). I was never increased.

 

I suspect low dose Sprycel will be very effective for many patients who take Sprycel currently and have molecular response. The risk in lowering your dose to test response is near zero. You can always go back up. I predict in a few years after additional research is concluded, the NCCN guidelines will be changed. Sprycel 70 mg will be the starting dose. It's moving in that direction. Also - Once MMR is achieved, doctors will be guided to lower dose to find the minimum necessary to keep patients responsive. Enlightened doctors are already doing this. 

[rct]

My oncologist never started me on 100 mg sprycel. He told me it's too high for most patients and that a lower dose - even a much lower dose can be as effective. He described it to me this way - Sprycel is a threshold drug. CML response to it is not dose dependent.  Once a minimum concentration is reached it's effect (if it is going to work at all) is dramatic. More is not better. More does not deepen response. 

 

Just like Gleevec.

 

rct

[scuba]

Just like Gleevec.

 

rct

 

 My comment above is with regard to Sprycel only. I have not read anything related to Gleevec or the other TKI's. 

[Gail's]

My latest pcr was .001. The lowest I've had! My onc talked to a colleague who encouraged her to stop Sprycel for one of her patients to get her feet wet with doing more in the future. I won't be part of a formal trial, but her idea is that perhaps when the load of cancerous WBCs is reduced, your own immune response may kick in to keep you healthy and undetectable.

I didn't think I'd even have a chance at stopping! Especially after gleevec didn't work well for me and I had to switch to Sprycel to get a deep response. I'm not at all afraid to stop because I know I'll be monitored closely and go right back on Sprycel if needed. I am a little concerned about withdrawal so I asked my onc to give me 20 mg tablets for the next 3 month cycle to taper down. I hope that helps.

[M.A.]

Great to hear about your 0.001 BCR ABL report Gail's. Are you on 50mg at the moment? 

[kat73]

Gail's - Good luck to you - I hopehopehope it works for you.

 

We seem to be in a confusing time.  I thought that, even outside of clinical trials, cessation was only to be tried after a one or two year period of Undetectable PCR's.  If you've only just arrived at the threshold (MR5, but still detectable), to try it now will be interesting to watch.  Maybe people can quit earlier.  In my case, I had been exactly where you are for about a year, when I had to quit Sprycel for a pleural effusion.  In just 5 weeks, my PCR jumped a log to 0.02 and at just 9 weeks I had lost MMR (another log) to 0.47.  I'm not worried - I'm sure I'll get back where I was eventually.  But it does go to show you that there is a possibility that "quitting too soon," might nix a durable cessation.  Of course, that could have absolutely nothing to do with it.  It could be something else entirely that dictates who can quit and who can't.  Anyway, I hope you are one that can!

[beno]

I'm looking forward to a lower dose of Sprycel.  I'm still on 100mg and I just found out today that I hit MMR right on the 1 year mark of being on it.

[Gail's]

M.A. Yes, dropped from 100 mg to 70 mg for 3 months. Now on 50 mg almost 6 months.
Kat73, yes, I worry about stopping too soon. That's why I'd like to drop to 20 mg for a couple of cycles and see what my numbers do. If I maintain my current low pcr on 20 mg I'm open to just staying there. Not afraid to try stopping but want to maximize chance of success too.

[scuba]

M.A. Yes, dropped from 100 mg to 70 mg for 3 months. Now on 50 mg almost 6 months.
Kat73, yes, I worry about stopping too soon. That's why I'd like to drop to 20 mg for a couple of cycles and see what my numbers do. If I maintain my current low pcr on 20 mg I'm open to just staying there. Not afraid to try stopping but want to maximize chance of success too.

 

I'm at 20mg now and have been for years (apart from my nine month cessation attempt). I am now preparing (special order) to go lower. I want to test how low a dose I can take and still keep my PCR numbers where they are ...

 

My goal is to get to 5mg daily. At 20mg I am borderline PCRU - still detected, but below the precision of the assay. I want to see if I can maintain response at 5mg and perhaps "train" my immune system to pick up the slack sort of speak.

 

You know ... there is another drug where 5mg is quite potent. I wouldn't know personally since I don't need that drug, but some here might know what drug I am referring.

[kat73]

Gail's - Yes, I am so hoping your plan works, not just for your benefit, but so I can go to my onc and say, "See?  A person can stay in a stable and very safe place on just 20 mg Sprycel, without it causing resistance." 

 

Scuba - Don't you wish we had some way of knowing exactly where that crucial number of leukemia-generating cells has to be in order for our immune systems to wipe every last one of them out?

[M.A.]

Gail's, your approach to lowering from 50mg to 20mg, rather than stopping, seems very sensible to me. It makes sense to go gradually with the body rather than stopping abruptly.

 

beno, your BCR ABL levels are coming down nicely. Looks like we were diagnosed around the same time, both had hydrea and both switched doctors. I had WBC 89 000 at diagnosis and 2% blasts.

 

I would still be taking 100mg Sprycel per day if I didn't have other health issues. I had protein levels increasing in my urine week by week on 100mg indicating kidney injury, leakage from the kidney tubules. This has now improved and stabilised on 50mg. Would it have done so over time on the 100mg? I'll never know.

 

I am pretty sure that if I had not had pre-existing diabetic nephropathy I would have been taken off Sprycel immediately. My haematologist said he thought it was just my diabetes causing the worsening proteinuria but my endocrinologist was adamant that it wasn't, and my nephrologist said that while the diabetes was contributing to some of the protein, the Sprycel was adding to it (he said there were two types of protein present, indicating two different origins of kidney damage). Nonetheless, all these doctors thought I should continue on 100mg Sprycel per day. I couldn't sleep at night due to worrying about it. I figured I was close to MMR, which to me meant the balance of risk had shifted, so reduced my own dose and made sure my BCR ABL was closely monitored.

 

For the record, my liver enzymes were elevated for the five months I was on full dose (not to the extent that doctors panic, but at least twice the upper limit of normal for each enzyme). This improved as soon as I reduced but took a year to come right back into the normal range, I had chest pains at  night on 100mg and I had horrible, excessive menstrual bleeding (never had this before in my life).

 

That was a big rant, but just to say I think we all have different risks and will have different responses to the various dosage levels of TKI, some needing more, some needing less. These factors might have nothing to do with it but I weigh 50kg, am 5 foot 2 and have a 37 year history of being very sensitive to medications (a little bit of drug goes a long way for me). These things also factored into my decision-making.

 

I'm grateful to everyone, including Scuba, who's shared their story on this board.

[Gail's]

I think part of my onc's eagerness to try cessation in me is my worsening kidney function. She's not horribly worried about it, but there was a definite change in my lab values. Went from my average gfr of 65 to 48 in one month. Considered stage 3 kidney disease but for me, labs had a dramatic change in a month. Creatinine went from average of .8 to 1.2 in that time although that's considered a normal creatinine level. Just a change for me.

[kat73]

Gail's - It's good she's alert.  One lab value isn't enough to know anything, of course, although it's enough to screw up your GFR, which scares people.  Doctors have told me, however, GFR is only good as a marker of progress or decline in patients they're already following for CKD and not of much use in general practice.  She'll want to watch the trend in your creatinine (and BUN).  If it continues, she might want to send you for a nephrologist for a workup.  This happened to me on Gleevec; was unaware of any problems with kidney function in the literature surrounding Sprycel.

[Gail's]

Kat73, I did read Sprycel can mess up kidneys too. But good news is that labs done this week were normal!

[kat73]

Relieved!  Good news. 

[mscl]

Just adding onto this feed for those that are hoping for a successful dose reduction. Quarterly bloodwork and appointment yesterday and I'm still undetectable on 20 mg Sprycel.

[kat73]

Terrific!  I've got to get back in to the PC doc to see if I have another effusion (on 50 mg Sprycel).  If I do, I'm definitely going to try 20 mg before I switch to anything else.

[M.A.]

Great news that you are still undetectable mscl especially after your experience with the severe rash.

 

Just got my latest BCR ABL results this morning.

 

Although I realise there is a lot of variability in sensitivity at this level I'm a bit disappointed. I was getting over-ambitious in my thinking... hoping to reach PCRU some time soon and then be able to reduce dose gradually again. But now I am just hoping to be able to stay on 50mg per day as more than that has a big impact on me in terms of side effects.

 

I see my doctor tonight and I am sure he will urge me to increase my dose.