15 replies to this topic

[duke01]

I am writing on behalf of my husband. He was diagnosed at age 50 with CML in chroinic phase and started on gleevac 400mg as most people do. He had slow response to this treatment his PCR moved from 79 to 40 in 6 months. During that time suffering with the typical muscle cramps. At 7 months of treatment he started with weight loss and increasing fatigue to discover his PCR had risen to 84 with enough circulating blasts to have accelerated phase CML. He had been using protonix daily for heartburn, this was stopped. He was switched to Sprycel 70 twice a day, which brought down his PCR to 0.3 over 4 months. He developed pleural effusions requiring drainage and dose was lowered to 70mg daily. He has maintained this dose for the last 10 months his PCR has stayed between 0.2 and 0.8 until last month moving to 1.2. He has had no further pleural effusions, mild muscle aches but mostly tolerating well. Doc suggests switching to Tasigna 400mg twice a day. We are leary to make another switch. Looking for feedback on possibly increasing Sprycel to 100mg or Tasigna at a lower dose?

[jmoorhou]

Two experts, Trey and Scuba will be responding soon. Trey is a Gleevec specialist and Scuba is Spycel.

[chriskuo]

Bosulif is another alternative to Sprycel and Tasigna.

[chevyflame]

I've been dealing with CML for four years starting with Sprycel @ 100mg, had severe side effects, dropped to 70mg then to 50mg then to 20mg every other day. I became undetectable during my second year and only saw an increase in my BCR-ABL numbers while on Gleevec

 

I have had to deal with severe bilateral pleural effusions for this entire time. In my third year my right side pleural effusion became loculated and no fluid is building. My oncologist suggested Gleevec to alleviate the pleural effusions.  This did not work as I was only on Gleevec @ 400 mg for forty days, had full body edema and pleural effusions to the point my eyeballs were swollen.

 

Changed my oncologist who suggested Tasigna @ 150mg. I was very unsure because the Sprycel  kept the CML undetectable.

I was extremely worried about new side effects.

 

This is my second month on Tasigna and have had good results so far. I had been draining 100ml daily at home by catheter on my left side but already the fluid levels are fluctuating, some days as low as 550mg. I feel so much better. My energy level has increased, I can actually taste food again, nausea is not as strong, I'm still undetectable and no other side effects have surfaced yet. It's amazing that I feel so much better because over time you become used to the terrible side effects. I'm very grateful for the TKI's and want to maintain the best quality of life possible.

 

Good luck on your CML journey, become as educated as possible and ask your oncologist every question you can think of. Our old oncologist wasn't too happy with all of the questions but it's my life. 

[ROMO]

Taking Sprycel 70mg twice a day will give you a over 30%

chance for pleural effusion. Because it's a high dose.

I think your Dr wanted to be more aggressive to bring the 

PCR numbers down.

 

 

Now that they are in the non threatening range things should get better.

 

Your husband might be a slow to respond type but he did respond.

He is in the safe enough zone and may need more time on this course.

 

.. this is just my 2cents.

 

Romo

[thatguy]

My vote, having no experience with Sprycel, but experience with Gleevec and Tasigna- I'd try 100MG Sprycel and retest a time or two, depending on the results. I've had my results fluctuate in that neighborhood of variance, but I wasn't ever classified in accelerated phase either...


A few people on here take 140mg too, so maybe that would be more effective?

[kat73]

duke - With all respect to thatguy, I would counsel NOT to increase the Sprycel, in light of your husband's documented pleural effusion AE.  Studies have determined that twice a day dosing of Sprycel (usually = 140 mg in a day) is associated with development of pleural effusions, which is probably why this happened to him.  Additionally, it is becoming more evident that even once a day 100 mg is possibly too high for some people, they develop pleural effusions, and that their CML is held in check pretty nicely at a lower dose (usually 70 or 50 mg).  I agree, it would be nice to hear from Trey, but I think a not bad idea for you would be to check another PCR (sooner than the usual 3 months) to see if this was an anomaly or a trend, before doing anything.  He didn't get a good response from Gleevec, possibly because of absorption issues due to the Protonix. So, it's possible you could keep Gleevec in reserve for someday, but since he DID have a good response to Sprycel, it might be worth it to at least see what the next PCR reveals.  Your onc is certainly following NCCN guidelines in recommending a drug switch now, however, as your husband has lost a log difference in his PCR and lost MMR. 

[kat73]

Addendum to the above:  I agree that if the next PCR confirms a loss of response a mutation test should be done.  I believe that is what the NCCN guidelines say, as well.

[Trey]

His response to high dosage Sprycel was very good, so the main issue is whether he could continue at a dosage above 70mg per day without PE and also control the CML better.  The 70mg per day has not caused PE for him, however the dosage seems to be inadequate since his blasts have been increased, so one possibility would be to try 100mg per day.  And although Sprycel is recommended once per day, if I had PE issues with it I would split the dosage to twice per day.  For some this might help, but research shows that results have been mixed with this approach.

 

The other option would be to switch to Tasigna to take a high dosage and avoid PE.  That is a reasonable approach.  Since his Onc recommends that, I see no reason to avoid that approach.  The PE has interfered with treatment.  For those who go into accelerated phase, they cannot allow side effects to cause periodic interruptions and dose reductions.  These drugs should be treated as tools which can be changed out for trying to find the one best suited to meet individual needs.  We all respond differently to each of them for various reasons.

 

So he could either try 100mg Sprycel or switch to high dosage Tasigna.  Overall, I would likely switch to Tasigna to try to avoid future dose reductions and drug stoppages.  Tasigna has an 18 hour half-life in the blood plasma while Sprycel has a 5 hour half life.  For some patients this increased availability of the drug in the plasma can be an advantage for Tasigna.

 

Here is some info about treating accelerated CML with Sprycel vs Tasigna:

https://www.texasonc...celerated-phase

 

Here is Sprycel clinical trial information which addresses some of the issues involved:

https://www.ncbi.nlm...les/PMC3520638/

Edited by Trey, 24 November 2017 - 09:48 AM.

[thatguy]

OP: his blasts WERE elevated earlier in treatment, correct? As in past tense? His latest pcr is 1.2%, and was recently fluctuating between .2 & .8 while on 70mg? Just to verify.

[duke01]

Thatguy you are correct! Currently awaiting a second opinion at Mayo with CML specialist. Will post the outcome of that visit, love that we can learn from each other. We are greatful for the feedback from everyone.

[duke01]

My husband had his visit at the Mayo. Recommendations are to repeat chest xray and bone marroow biopsy. If the biopsy looks ok, no mutations or sign that he is progressing to the accelerated phase will continue w TKI treatment. If there is little to no fluid on the lungs will increase Sprycel to 100mg day. If lungs have fluid then switch to Tasigna 300mg twice a day. Will know more next week hoping to get these tests done quickly. Will post again when we know more.

[kat73]

duke - Sounds like your husband is in good hands.  Thanks for posting the ongoing story - it's helpful to everybody.  I'll be looking for the results next week and hope there is good news for moving ahead into a routine.  I think that a great deal of the troubles we have are because nothing ever seems settled or stays the same.  There are always new questions and new problems, most of them with no answers except "try this and see."  It's hard to knuckle down and get used to something and put it in perspective in order to go on with life when it all keeps changing.  Hang in there!

[duke01]

Chest xray showed minimal fluid. Bone marrow was a dry tap, disappointing. PCR 1.3, CBC normal, CMP normal. Increased Sprycel to 100mg daily, recheck labs in 1 month. Fingers crossed he tolerates this well and PCR drops. We appreciate everyones feedback.

[kat73]

duke - Frustrating to still have to wait and see, but soon you will have a clear path forward.  Enjoy the holidays.  Time will tell all.  Keep us posted!

[r06ue1]

Was doing some reading on GVAX being used in trials of Accelerated Phase CML...

 

GVAX had some positive results in trials:  

"The GVAX Leukemia vaccine was given to 19 CML patients with measurable cancer cells, despite taking Gleevec for at least one year (range 13-53 months). Each patient was given a series of four vaccines administered in three-week intervals while remaining on a stable dose of Gleevec. After a median of 72 months of follow-up, the number of remaining cancer cells declined in 13 patients, eight of whom had increasing disease burden before vaccination. Twelve patients reached their lowest levels of residual cancer cells to date following vaccination. In seven patients, CML became completely undetectable."

 

http://livingwithcml...ccine-news.html

 

But alas, Big Pharma dropped it:  

"Unfortunately, the pharmaceutical company sponsoring this study has cancelled plans for further testing of this agent."

https://www.texasonc...celerated-phase

 

But I did find further in the article some good news:  

"Fortunately, other researchers are also developing vaccines for the treatment of CML. Researchers at the Memorial Sloan-Kettering Cancer Center developed and are testing a vaccine which has proven safe and effective in developing an immune responses in patients with CML."  

 

Pinilla-Ibarz J, Cathcart K, Korontsvit T, et al. Vaccination of patients with chronic myelogenous leukemia with bcr-abl oncogene breakpoint fusion peptides generates specific immune responses. Blood 2000;95:1781-1787.

 

Maybe check with Memorial Sloan-Kettering Cancer Center to see if that trial is still ongoing.