31 replies to this topic

[FalseAlarm]

Hello everyone, I am a CML patient from Malaysia (diagnosed six months ago). I was diagnosed with AP so I was put on Tasigna soon after diagnosis, and it quickly brought down my blood count to normal level in 2 months time. And today I found out my wbc has  climbed up to 42.8 (it was within normal range previously), I was very worried but my doctor told me to wait for the results of BMB and in the meantime continue taking Tasigna and he said he needs to see what the BMB results show before he decides the next course of action.

Is it normal for the wbc to suddenly jump up to 40+ while on TKI? and should I be worried?

[Trey]

It is not normal to have such a jump in WBC at this point.  You will need to change drugs.  The BMB will likely show similar issues, but will not reveal the root cause.  You should ask the doctor to perform a Kinase Mutation Test to see if you have a kinase mutation interfering with the Tasigna.  That is important to determine which new drug to use.  But you should be switched to another TKI drug right away.  I would prefer Sprycel.  If a kinase mutation called T315i is discovered you would need a different drug named Iclusig (Ponatinib).

[FalseAlarm]

I'll be going back to the hospital in a week time, will see what the doctor has to say after he sees the BMB results and he did say something about switching drugs in case abnormal results show up. I don't know if Sprycel is available in Malaysia though. I was informed during counseling that there are only two CML drugs (Gleevec and Tasigna) in Malaysia, but that was six months ago, so things might have changed now, but I'm not sure. Will keep you posted on the progress...

[Trey]

Gleevec can sometimes work better than Tasigna for some patients, but that is rare.

You may also want to contact the CML Asian Support Group and ask about drug availability options.

http://www.cml-liteh....com/index.html

[August1]

I have also read that Sprycel can be more effective that Gleevac for CML in accelerated phase. Not sure if that is a possibility for you.

[FalseAlarm]

Hi Trey, sorry for the late reply, I've been busy last month dealing with school's stuff.

I've done the test a month ago. I got the result today and it shows E255k in addition to T315i. My doctor tells me to take interferon and hydroxyurea while he's enrolling me into the compassionate use program for ponatinib in Singapore. I hope it gets through cos he seems trying to push me into doing a BMT

[FalseAlarm]

I've done the mutation test and the results aren't promising, in fact I've been on sprycel for the past couple of weeks and it did nothing to bring the WBC count back to normal and it rose to 70 today.

[hannibellemo]

FalseAlarm,

I'm very sorry to hear about your point mutation diagnosis. I've attached a chart that shows which mutations exhibit a sensitivity to Sprycel and Tasigna, for some reason it doesn't show anything for Gleevec and it was probably published before Iclusig which seems to be your best bet at this point in terms of TKIs.  While you are waiting to hear about compassionate use has your onc talked about starting the process for a BMT? It might cut down on some of the wait time if you begin looking for a match now.

http://www.nature.co...u2009193t1.html

Please let us know how you are doing and I will keep you in my thoughts and prayers.

Pat

[Trey]

The T315i is generally resistant to all TKI drugs except Ponatinib (Iclusig).  Short term the hydroxyurea (HU) can keep the WBC lower, but that will not work over the longer term.  Be careful to have your blood counts monitored very closely since HU can wipe out your cell counts.  Your long term options are Ponatinib (Iclusig) or BMT, and some people (very few) can respond to interferon alone, but the treatment can make many people feel sick constantly. 

[FalseAlarm]

My oncologist says IFN is the temporary option until I get ponatinib. Hopefully I will be accepted into the program but I'm rather worried after reading the news that the enrollment has been halted by FDA due to reports of blood clotting. Does the decision affect all trials across the globe or trials in USA only?

[Susan61]

Hi:  Sorry your having so much trouble with your TKI drug.  I think I would try the Iclusig before going for the BMT.  I wish you well on whatever is decided.  My thoughts and prayers are with you also along with Pat.

I think we all need to pray for them to come up with something else real quick thats even better than a TKI to avoid BMT.

Susan

[FalseAlarm]

Hi, hannibellemo and Susan61, first of all thanks for the support, really appreciate it. My onc is all prepped for a BMT now. But he intends to  put me on ponatinib first to buy enough time for me before a compatible  donor is identified. He says he'll me let me know about the status of enrollment for the compassionate use program three weeks later (hopefully sooner), and well, I hope it's good news.

[FalseAlarm]

http://www.onclive.c...dy-Discontinued

It's official, Ariad has terminated its clinical trial for ponatinib. I guess BMT is my only option now.

[hannibellemo]

False alarm,

Don't give up hope! As I read this, the study that was terminated was looking at Iclusig as a first line drug, the people in the trial had not been treated with any other drug before this. I believe it is still available for those with the T315i mutation.

Pat

[Trey]

In the meantime you could try Omacetaxine Mepesuccinate (also called Homoharringtonine or Synribo) instead of the hydroxyurea.  It is approved for CML in the U.S., and is a chemotherapy drug not a TKI drug.  It has shown some benefit for those with T315i, although a BMT would likely still be needed.  But it could delay the need for a BMT, and maybe something else might be developed, or Ponatinib may become available again.  Either way this would work better than hydroxyurea.

http://en.wikipedia....e_mepesuccinate

http://bloodjournal....20/13/2573.long

[Happycat]

Actually, ponatinib is still available for patients who have failed other TKIs. The study was looking at ponatinib as a first line treatment for CML, not just those with the T315I mutation.  The risk of blood clots is too high to use it in those who may respond just as well to a different TKI, so they stopped that particular study. But patients with a demonstrated need, such as the T315I mutation, should be able to get it. In those cases, the risk of a blood clot is worth it, since it's more important to get the CML under control. Don't give up hope just yet. I don't know how readily you can get it in Malaysia, and it wouldn't surprise me if the failure of the clinical trial led to a slight pause in approvals for those who truly need it, but I think anyone with a demonstrated need should still be able to get it.

It is likely that patients on ponatinib may end up taking a low dose anti-coagulant, maybe heparin or clopidogrel, as a prophylactic against clots.

I hope you get the situation cleared up soon. It must be terribly worrying for you.

My best to you,

Traci

[hannibellemo]

Trey,

So iclusig is not at this point available even to those who have been taking it since it was approved (Beth?!) not just to the Epic and other trial participants? It is not available for compassionate use?

Pat

[Trey]

I did not say either way.  Iclusig is still available to long term users, and for new patients who qualify for second line CML treatment under FDA guidelines.  New enrollments in ponatinib/Iclusig clinical trials are on hold, and some trials for non-CML diseases have been put on hold.  FA's issue is she [edit correction: he] lives in Malaysia where Iclusig is not an approved drug.  Compassionate use is up to ARIAD to decide as far as I can tell, but less likely for those outside U.S. would be my guess.  But the Onc should try and see what happens. 

Message was edited by: Trey Fox

[FalseAlarm]

Hi all,

I just went to the hospital and as I expected, they (Ariad) have stopped enrolling new patients into the program or as my onc would like to put it - Closed. My onc is moving forward with the BMT and according to him it would take on average 6 weeks to find a donor, in the meantime I will continue to take IFN and HU. By the way, I am a male, I do not know what gave Trey the impression that I am a female (my choice of words I guess?), but it is alright .

[FalseAlarm]

Hi Trey,

I do not think I can get synribo here in Malaysia. I can probably get it in Singapore, but since I'm not their citizen, cost is a concern for me and it would probably cost me an arm and leg just to get a one month supply. Iclusig is not an approved drug in Malaysia, neither it is in Singapore. Ariad is doing clinical trial there and my onc told me he sent two Malaysian patients over to the program before. Too bad I was not accepted so I have no choice but to move forward with the BMT.