8 replies to this topic

[stephiericks]

My husband was diagnosed with CML in early August and we just received the results from his 6 month bone marrow test.  Not what we had hoped and trying hard to stay positive - its so easy to think the worst and I'm hoping the answers to a few lingering questions will help.

His blood work test showed great hope and his numbers all moved to the normal range quickly.  He has had very little side effects - leg cramps here and there and chills.  The bone marrow test showed that 10 of the 20 still showed the Philadelphia, a lot more than the optimal 30% or less.  His doctor is switching him to Sprycel and he's getting tested for the genetic mutation that resists all drug treatments (sorry, don't remember its name).  Here are my questions:

1) I know that many people switch treatments because of intolerance to side effects.  How many have to change treatments because of suboptimal response? (Our oncologist has had 10 patients and only one has had to change from Gleevec)

2) What is the success rate for the 2nd treatment drug (in this case Sprycel) when switching due to suboptimal response?

3) What percentage of patients have the genetic mutation that resists all drug therapies?

There always seem to be questions I think up after we leave the appointment and I really appreciate any answers you can help me with - thank you!

My best,

Stephanie

[GerryL]

Hi Stephanie,

Welcome to the discussion board - I'll leave Trey and the others to talk to you about the numbers, but I would like to say there are a few people here who have switched drugs due to subtominal response. Sprycel and Tasigna provide a quicker response than Gleevec.

[scuba]

Hi Stephanie,

I had suboptimal response with Gleevec. My FISH levels dropped at first then went back to 100%. I switched to Sprycel and it had an immediate impact. Within a short time my FISH levels went to zero but not in the usual way. I could only stay on Sprycel 70mg for two weeks due to severe myelosuppression brought on by the Sprycel. I had to stop Sprycel (and not take any TKI)  for 3 months while my blood counts recovered naturally (no stimulation of the bone marrow). During that time, however, my FISH continued to fall to zero even though I was off the drug*. My PCR, however, did not fall but remained around 55% (intl. scale) even increasing a small amount. After 3 months, I was re-started on Sprycel but at a much lower dose of 20mg. I was able to stay on the drug without interruption. My PCR began to fall quickly. After seven months I went from 55% to 0.12% PCR and then 3 months after that my PCR fell to 0.06% (Feb'12 data). Dr. Cortes tells me I am in Major Molecular Remission and he does not want to increase my dose even though I asked him to increase it. He told me "more is not better". So I continue to take 20mg. Sprycel.

The most important thing about these drugs is that your trend is downward for PCR and FISH = zero. And once you get a zero in your PCR readings (  .0) you have a very good prognosis. Add a few more zero's to the right of the decimal point - even better.

Chances are very good that:

1: Your husband does not have the t315i mutation (even if he did, there is a treatment for that)

2. Your husband will respond to either Sprycel or Tasigna very well.

Switch to Sprycel (or Tasigna) and measure response at 3 months. No real need for a mutation test until after you try one of these drugs.

Hope this is useful to you.

p.s. *When I switched to Sprycel at 70mg, I also began a Curcumin supplement regimen. Curcumin is an herb that interferes with CML cells ability to replicate and stay alive. It is possible, but no one knows with any certainty, that the Curcumin impacted the CML along with the Sprycel. There is some data on Colon Cancer that suggests Curcumin + Sprycel is more effective combined. I am pleased that I am able to stay on 20mg. Sprycel and still achieve a deep response. I have no side affects that I can feel as a result.

[hannibellemo]

Hi, Stephanie,

I know this is a worrisome time for you both. I thought I would tell you about my experience with Gleevec. I was dxed 12/2008. Started Gleevec 1/09. Mayo tends to use FISH rather than PCR for testing until CCyR status is achieved and I saw my onc every 4 months, not three. At dx my FISH was 98%, pretty normal, and I had a fairly large cancer load - WBC 3.5 k and Platelets of 1.5 m, spleen very enlarged. At four months I had reached CHR, but only minor cytogenetic response of 75%. Very disappointing but still within the guidelines. At 8 months my FISH went down to 4% (within the margin of error for CCyR) but they also determined through extremely elevated results on my liver function tests that I probably would not be able to continue on G so after a 7 week break to allow my AST/ALTs to return to normal I started Sprycel.

I had very few adverse side effects on G (if you don't count the liver ) and I have a love/hate relationship with Sprycel, but it does work for most people. I wouldn't hesitate to switch although it seems as though it go either way for your husband at this point. I have been MMR on Sprycel for almost 2 years, I don't know the exact percentage of people with positive response rates to Sprycel as 2nd line treatment but I know it is quite high. There is every reason to think it will work for your husband should he decide to switch.

This link to a fact sheet on Ponatinib indicates that 15-20% of all mutations are the T315i.  It also says that within the first 7 years on Gleevec approximately 40% will move on to 2nd line therapies due to loss of response or intolerance. http://www.ariad.com..._Fact_Sheet.pdf

It sounds like you are aware of the guidelines, but just in case here they are: http://www.nccn.org/.../index.html#/1/

Hope this helps a little.

Good luck!

Pat

[Marnie]

Hi, Stephanie. . .

I switched from Gleevec to Sprycel due to suboptimal response.  I took a 5 day drug break after stopping Gleevec and then began Sprycel at half dose (50 mg) for 5 days before starting at full dose (100 mg).  I would highly recommend that you talk to your husband's oncologist about this option.  I had heard horror stories about horrific headache issues when switching to Sprycel.  I had about a week, maybe 2 weeks, of minimal headaches.  Other than that, not many side effects to speak of.  I feel a LOT better on Sprycel and my PCR results dropped significantly after switching to Sprycel.  I'm still not PCRu after a year on Sprycel, which is a frustration, but but I think I'm just one of those people who may never get there, or who will get there very, very slowly. 

I had the mutation testing done as well, and had an insignificant mutation. . .not one of the bad ones.  Sprycel and Tasigna are typically effective with most mutations, though not the dreaded T315i.  Luckily, Ponatinib and Bosutinib seem to be doing well with that mutation, and other options are in the pipeline. 

Please feel free to send me a private message if you'd like my personal e-mail for questions, though Trey is the resident expert and will be able to answer any questions that you have.  He can probably answer them better than your husband's oncologist can.

All the best,

Marnie

[Trey]

So far your husband is responding to Gleevec, just not quickly.  You correctly label this a suboptimal response, not drug failure.  Some can overcome this with higher dosage Gleevec, or by switching drugs.  A switch from Gleevec to a second line drug is a good strategy in a case like this.

The 40% statistic for patients moving to a second line drug is about right if side effects issues are included, but less for actual failure or suboptimal response.  The reasons for suboptimal response can be several, but kinase mutations are one of the lesser causes.  But doing the kinase mutation test is still a good idea.  More patients have other reasons, including decreased drug uptake into the cells due to low hOct-1 (a "cell pump" that brings proteins and drugs into the cell).  Since the second line TKI drugs use alternative drug uptake methods they can easily overcome this issue.  Also, sometimes the leukemic cells can use alternative survival pathways, and Sprycel can often overcome that issue.  And Sprycel binds differently than Gleevec or Tasigna, so can work when the others do not.  So there are a number of reasons why the second line drugs can perform better than Gleevec in some people. 

The second line drugs will work for most patients who do not do well on Gleevec.  The stats are better for those who a just slow responders, and not a complete failure.  Since your husband achieved the initial CHR goal and has actually responded to Gleevec, the chances of Sprycel working well for him are high.

[stephiericks]

It was so nice to wake up and have these thoughtful and very helpful responses - answers my questions and definitely makes me feel better!  Thank you so very much

[Judy2]

Hi Stephanie,

I was on Gleevec 200mg, half the usual dose because of another medical condition, for 5 months amd my PCR rose yet only after 5 weeks on Sprycel 50mg, again half the standard dose, my PCR has started to drop. We are very lucky to have more than one TKI and I am confident that one will work for him.

Judy

[Tedsey]

Dear Stephanie,

I was on Gleevec 9 months and due to sub-optimal response, I switched to Sprycel.  I have never been tested for any mutations.  Before my drug switch to Sprycel, I had 3 flat PCRs and did not have a complete cytogenic response (CCR where all cells in a sample look normal).  After 3 months on Sprycel, I had a CCR.  Some people just respond better to one drug over the other.  Best of luck with the new drug.

Tedsey