Re: mutations and resistance

[Guest guest]

Hi Kathy:

 

Who is your Dr and where are you treated? I came of gleevec because of

intolerence and went on dastinib. I would push for mutation testing. Better to

know know then later.And if you have a mutation, which drug would be better at

treating it.

 

Blessings

From: kathymhyland <kathymhyland@...>

Subject: [ ] mutations and resistance

Date: Monday, December 8, 2008, 11:12 PM

Hi, everyone. I'll be seeing a new doctor on Weds, a colleague of my

current dr, to discuss changing meds. I need some help understanding

gleevec resistance and mutations. My Dr believes I am " failing "

gleevec, but that we don't need to do the mutation test. She believes

that since I did well on gleevec for 3 years, I could not have a

mutation. I had assumed that the mutations were acquired--an

adaptation/evolutio nary thing. Perhaps we are both right. I really

want to push for this mutation test, so any information that would help

me plead my case is appreciated. Without a mutation present, how do

you explain gleevec " resistance? " And finally, I know each new drug

binds well to specific mutations. Without that guideline, how do you

choose which drug to use? I now she's leaning toward dasatinib.

Thanks for your help--have a great day!

[Guest guest]

Thanks,

 

I live in Nashville, and this doctor is my local hem/onc who has limited

experience treating cml.  On Weds I will see one of her colleagues at TN

oncology who was trained at MD and actually  is a transplant doctor. 

What is your history, if you don't mind me asking?  Did you ever do well with

gleevec?  And how are your responses and side effects on dasatinib?

 

Thanks,

Kathy

From: kathymhyland <kathymhyland>

Subject: [ ] mutations and resistance

groups (DOT) com

Date: Monday, December 8, 2008, 11:12 PM

Hi, everyone. I'll be seeing a new doctor on Weds, a colleague of my

current dr, to discuss changing meds. I need some help understanding

gleevec resistance and mutations. My Dr believes I am " failing "

gleevec, but that we don't need to do the mutation test. She believes

that since I did well on gleevec for 3 years, I could not have a

mutation. I had assumed that the mutations were acquired--an

adaptation/evolutio nary thing. Perhaps we are both right. I really

want to push for this mutation test, so any information that would help

me plead my case is appreciated. Without a mutation present, how do

you explain gleevec " resistance? " And finally, I know each new drug

binds well to specific mutations. Without that guideline, how do you

choose which drug to use? I now she's leaning toward dasatinib.

Thanks for your help--have a great day!

[Guest guest]

hi kathy, i think we are neighbors. i live in franklin, tn. i go to a

dr. with vanderbilt.  jean

________________________________

From: Kathy Hyland <kathymhyland@...>

Sent: Tuesday, December 9, 2008 16:16:29

Subject: Re: [ ] mutations and resistance

Thanks,

 

I live in Nashville, and this doctor is my local hem/onc who has limited

experience treating cml.  On Weds I will see one of her colleagues at TN

oncology who was trained at MD and actually  is a transplant doctor. 

What is your history, if you don't mind me asking?  Did you ever do well with

gleevec?  And how are your responses and side effects on dasatinib?

 

Thanks,

Kathy

From: kathymhyland <kathymhyland@ ..com>

Subject: [ ] mutations and resistance

groups (DOT) com

Date: Monday, December 8, 2008, 11:12 PM

Hi, everyone. I'll be seeing a new doctor on Weds, a colleague of my

current dr, to discuss changing meds. I need some help understanding

gleevec resistance and mutations. My Dr believes I am " failing "

gleevec, but that we don't need to do the mutation test. She believes

that since I did well on gleevec for 3 years, I could not have a

mutation. I had assumed that the mutations were acquired--an

adaptation/evolutio nary thing. Perhaps we are both right. I really

want to push for this mutation test, so any information that would help

me plead my case is appreciated. Without a mutation present, how do

you explain gleevec " resistance? " And finally, I know each new drug

binds well to specific mutations. Without that guideline, how do you

choose which drug to use? I now she's leaning toward dasatinib.

Thanks for your help--have a great day!

[Guest guest]

Wow--yes we are.  I live off 65 in the Brentwood area.  Good to know you!  Tell

me about your history and your dr at VUMC.  I was dx'd in May 05 and was hooked

up with TN Onc after my ER diagnosis at St .  My Dr doesn't have much

experience with cml, so I envision a move to Vanderbilt.  Are you happy there?  

Thanks for posting, Jean.  It really made my day!

 

Kathy

From: kathymhyland <kathymhyland@ ..com>

Subject: [ ] mutations and resistance

groups (DOT) com

Date: Monday, December 8, 2008, 11:12 PM

Hi, everyone. I'll be seeing a new doctor on Weds, a colleague of my

current dr, to discuss changing meds. I need some help understanding

gleevec resistance and mutations. My Dr believes I am " failing "

gleevec, but that we don't need to do the mutation test. She believes

that since I did well on gleevec for 3 years, I could not have a

mutation. I had assumed that the mutations were acquired--an

adaptation/evolutio nary thing. Perhaps we are both right. I really

want to push for this mutation test, so any information that would help

me plead my case is appreciated. Without a mutation present, how do

you explain gleevec " resistance? " And finally, I know each new drug

binds well to specific mutations. Without that guideline, how do you

choose which drug to use? I now she's leaning toward dasatinib.

Thanks for your help--have a great day!

[Guest guest]

I am curious to know who the transplant doctor is. When you get his/her name

please tell us.

Thanks, Anita

________________________________

From: Kathy Hyland <kathymhyland@...>

Sent: Tuesday, December 9, 2008 4:16:29 PM

Subject: Re: [ ] mutations and resistance

Thanks,

 

I live in Nashville, and this doctor is my local hem/onc who has limited

experience treating cml.  On Weds I will see one of her colleagues at TN

oncology who was trained at MD and actually  is a transplant doctor. 

What is your history, if you don't mind me asking?  Did you ever do well with

gleevec?  And how are your responses and side effects on dasatinib?

 

Thanks,

Kathy

From: kathymhyland <kathymhyland>

Subject: [ ] mutations and resistance

groups (DOT) com

Date: Monday, December 8, 2008, 11:12 PM

Hi, everyone. I'll be seeing a new doctor on Weds, a colleague of my

current dr, to discuss changing meds. I need some help understanding

gleevec resistance and mutations. My Dr believes I am " failing "

gleevec, but that we don't need to do the mutation test. She believes

that since I did well on gleevec for 3 years, I could not have a

mutation. I had assumed that the mutations were acquired--an

adaptation/evolutio nary thing. Perhaps we are both right. I really

want to push for this mutation test, so any information that would help

me plead my case is appreciated. Without a mutation present, how do

you explain gleevec " resistance? " And finally, I know each new drug

binds well to specific mutations. Without that guideline, how do you

choose which drug to use? I now she's leaning toward dasatinib.

Thanks for your help--have a great day!

[Guest guest]

Dr. Couriel--he works at Cannon Cancer Ctr--will let you know how

it goes.

 

Thanks,

Kathy

From: kathymhyland <kathymhyland>

Subject: [ ] mutations and resistance

groups (DOT) com

Date: Monday, December 8, 2008, 11:12 PM

Hi, everyone. I'll be seeing a new doctor on Weds, a colleague of my

current dr, to discuss changing meds. I need some help understanding

gleevec resistance and mutations. My Dr believes I am " failing "

gleevec, but that we don't need to do the mutation test. She believes

that since I did well on gleevec for 3 years, I could not have a

mutation. I had assumed that the mutations were acquired--an

adaptation/evolutio nary thing. Perhaps we are both right. I really

want to push for this mutation test, so any information that would help

me plead my case is appreciated. Without a mutation present, how do

you explain gleevec " resistance? " And finally, I know each new drug

binds well to specific mutations. Without that guideline, how do you

choose which drug to use? I now she's leaning toward dasatinib.

Thanks for your help--have a great day!

[Guest guest]

Hi Kathy,

Sorry for the delay in responding, it's crazy this time of year and I

feel as if I'm running around like the proverbial chicken with its

head cut off.

Some mutations are acquired while others are there from the beginning

so you're both right. You could very well have acquired one recently

and knowing this information will allow you to choose the right drug

option.

If you need some journal articles supporting your case, let me know

and I'll try to dig them up but seeing as you were seeing your doctor

today, I wonder if it's too late?

Tracey

>

> Hi, everyone. I'll be seeing a new doctor on Weds, a colleague of

my

> current dr, to discuss changing meds. I need some help

understanding

> gleevec resistance and mutations. My Dr believes I am " failing "

> gleevec, but that we don't need to do the mutation test. She

believes

> that since I did well on gleevec for 3 years, I could not have a

> mutation. I had assumed that the mutations were acquired--an

> adaptation/evolutionary thing. Perhaps we are both right. I really

> want to push for this mutation test, so any information that would

help

> me plead my case is appreciated. Without a mutation present, how

do

> you explain gleevec " resistance? " And finally, I know each new

drug

> binds well to specific mutations. Without that guideline, how do

you

> choose which drug to use? I now she's leaning toward dasatinib.

> Thanks for your help--have a great day!

>

[Guest guest]

Hi Kathy I live in Crossville,My onc is in Oak Ridge Dr Foust.

Dec 23 is my 3 year term of treatment. I reached PCRU 11/12/08

600 Gleevec.I have been going to a local onc that known 's nothing about CmL

pleased with change even if I drive 38 miles.

________________________________

From: Kathy Hyland <kathymhyland@...>

Sent: Tuesday, December 9, 2008 4:16:29 PM

Subject: Re: [ ] mutations and resistance

Thanks,

 

I live in Nashville, and this doctor is my local hem/onc who has limited

experience treating cml.  On Weds I will see one of her colleagues at TN

oncology who was trained at MD and actually  is a transplant doctor. 

What is your history, if you don't mind me asking?  Did you ever do well with

gleevec?  And how are your responses and side effects on dasatinib?

 

Thanks,

Kathy

From: kathymhyland <kathymhyland>

Subject: [ ] mutations and resistance

groups (DOT) com

Date: Monday, December 8, 2008, 11:12 PM

Hi, everyone. I'll be seeing a new doctor on Weds, a colleague of my

current dr, to discuss changing meds. I need some help understanding

gleevec resistance and mutations. My Dr believes I am " failing "

gleevec, but that we don't need to do the mutation test. She believes

that since I did well on gleevec for 3 years, I could not have a

mutation. I had assumed that the mutations were acquired--an

adaptation/evolutio nary thing. Perhaps we are both right. I really

want to push for this mutation test, so any information that would help

me plead my case is appreciated. Without a mutation present, how do

you explain gleevec " resistance? " And finally, I know each new drug

binds well to specific mutations. Without that guideline, how do you

choose which drug to use? I now she's leaning toward dasatinib.

Thanks for your help--have a great day!

[Guest guest]

Hi,

 

It's always good to hear from you.  I had the appt today, and it was a blessing

b/c we communicated so well.  As was my thought, the driving test result is the

positive cytogenetic test that showed one pos cell among the 20 analyzed.  So it

appears that the only option I don't have is to stay the course.  Blood was

taken for the mutation test.  Do you know how this is conducted and how long it

takes?  With those results in hand, we will change treatment.  He feels that

without a good (not sure how that will be defined) molecular response in 6

months, we'll look at transplant.  He said it would be best to proceed while I'm

" young and otherwise healthy. "   I asked him if he knew how old I was, b/c at 46

I thought I was considered " old " for transplant purposes.  Very relieved to know

that was not his opinion.

 

The latest newsletter from MDACC said that 50% of gleevec resistance was due to

mutation.  Where does the other 50% come from?  And if your resistance is NOT

due to mutation, would dose escalation of gleevec be worthy of a try?  And

within the 50% of mutations, any idea what % is due to that nasty T3151?  Sorry

for all the questions, but your help is invaluable.

 

This time of year is incredibly busy, so please don't feel rushed, but I would

love to know what articles you recommend.  Have a great day!

 

Thanks,

Kathy

From: Tracey <traceyincanada@...>

Subject: [ ] Re: mutations and resistance

Date: Wednesday, December 10, 2008, 2:00 PM

Hi Kathy,

Sorry for the delay in responding, it's crazy this time of year and I

feel as if I'm running around like the proverbial chicken with its

head cut off.

Some mutations are acquired while others are there from the beginning

so you're both right. You could very well have acquired one recently

and knowing this information will allow you to choose the right drug

option.

If you need some journal articles supporting your case, let me know

and I'll try to dig them up but seeing as you were seeing your doctor

today, I wonder if it's too late?

Tracey

>

> Hi, everyone. I'll be seeing a new doctor on Weds, a colleague of

my

> current dr, to discuss changing meds. I need some help

understanding

> gleevec resistance and mutations. My Dr believes I am " failing "

> gleevec, but that we don't need to do the mutation test. She

believes

> that since I did well on gleevec for 3 years, I could not have a

> mutation. I had assumed that the mutations were acquired--an

> adaptation/evolutio nary thing. Perhaps we are both right. I really

> want to push for this mutation test, so any information that would

help

> me plead my case is appreciated. Without a mutation present, how

do

> you explain gleevec " resistance? " And finally, I know each new

drug

> binds well to specific mutations. Without that guideline, how do

you

> choose which drug to use? I now she's leaning toward dasatinib.

> Thanks for your help--have a great day!

>

[Guest guest]

Hi Kathy,

I'm so glad your appointment went well and that he did the mutation

testing. I really don't know how long it takes to get results,

perhaps someone who's had it will pipe in and let you know.

The only thing that concerns me is his seemingly eagerness to jump to

transplant. I'd love to know how he defines a " good molecular

response " but I'm thinking that 6 months is a bit overzealous if he's

looking for a molecular response.

It's taken many of us years to get a good molecular response and

studies have shown that molecular responses do get better after years

of treatment (that's right, I said YEARS of treatment, not months).

I'll try to dig up some papers on mutations later as right now I'm on

my way out the door. I will say though, that the nasty T315I

mutation is very rare.

Also, most doctors now feel that it would be better to go to a new

drug rather than increase the dose of Gleevec just because of the

side effect profile. Most people have difficulty tolerating the

800mg dose of Gleevec but most can tolerate the standard doses of the

new drugs which are known to be effective so why risk quality of life

issues when there are alternatives available.

More later,

Tracey

>

> From: Tracey <traceyincanada@...>

> Subject: [ ] Re: mutations and resistance

>

> Date: Wednesday, December 10, 2008, 2:00 PM

>

>

>

>

>

>

> Hi Kathy,

>

> Sorry for the delay in responding, it's crazy this time of year and

I

> feel as if I'm running around like the proverbial chicken with its

> head cut off.

>

> Some mutations are acquired while others are there from the

beginning

> so you're both right. You could very well have acquired one

recently

> and knowing this information will allow you to choose the right

drug

> option.

>

> If you need some journal articles supporting your case, let me know

> and I'll try to dig them up but seeing as you were seeing your

doctor

> today, I wonder if it's too late?

>

> Tracey

>

> --- In groups (DOT) com, " kathymhyland " <kathymhyland@ ...>

wrote:

> >

> > Hi, everyone. I'll be seeing a new doctor on Weds, a colleague of

> my

> > current dr, to discuss changing meds. I need some help

> understanding

> > gleevec resistance and mutations. My Dr believes I am " failing "

> > gleevec, but that we don't need to do the mutation test. She

> believes

> > that since I did well on gleevec for 3 years, I could not have a

> > mutation. I had assumed that the mutations were acquired--an

> > adaptation/evolutio nary thing. Perhaps we are both right. I

really

> > want to push for this mutation test, so any information that

would

> help

> > me plead my case is appreciated. Without a mutation present, how

> do

> > you explain gleevec " resistance? " And finally, I know each new

> drug

> > binds well to specific mutations. Without that guideline, how do

> you

> > choose which drug to use? I now she's leaning toward dasatinib.

> > Thanks for your help--have a great day!

> >

>

>

>

>

>

>

>

>

>

>

>

>

>

>

>

>

[Guest guest]

Hi ,

It's good to hear from you.  Glad to know you are happy with your doctor, and

that your treatment is going so well.  How did you find your onc?  Have you been

on 600mg the whole time?  Thanks!

Kathy

From: kathymhyland <kathymhyland>

Subject: [ ] mutations and resistance

groups (DOT) com

Date: Monday, December 8, 2008, 11:12 PM

Hi, everyone. I'll be seeing a new doctor on Weds, a colleague of my

current dr, to discuss changing meds. I need some help understanding

gleevec resistance and mutations. My Dr believes I am " failing "

gleevec, but that we don't need to do the mutation test. She believes

that since I did well on gleevec for 3 years, I could not have a

mutation. I had assumed that the mutations were acquired--an

adaptation/evolutio nary thing. Perhaps we are both right. I really

want to push for this mutation test, so any information that would help

me plead my case is appreciated. Without a mutation present, how do

you explain gleevec " resistance? " And finally, I know each new drug

binds well to specific mutations. Without that guideline, how do you

choose which drug to use? I now she's leaning toward dasatinib.

Thanks for your help--have a great day!

[Guest guest]

Hi Tracey,

Thanks again for a great post.  And thanks for bringing my back to earth about

transplant.  It is absolutely the last thing I want, and my experience with any

surgeon has always been that they advocate for surgery.  I guess my fear would

be that relapse could bring unpredictable disease progression, and if I had to

face transplant I think I'd like to do it before I got too sick or weak.  Do we

know how this progresses?  If I was early chronic phase at dx in 05, would  I

land there  again?

 

And your comment about high dose gleevec made great sense.  Quality of life is

so important, and these side effects can be rough.

 

Thanks again,

Kathy

From: Tracey <traceyincanada@...>

Subject: [ ] Re: mutations and resistance

Date: Thursday, December 11, 2008, 12:43 PM

Hi Kathy,

I'm so glad your appointment went well and that he did the mutation

testing. I really don't know how long it takes to get results,

perhaps someone who's had it will pipe in and let you know.

The only thing that concerns me is his seemingly eagerness to jump to

transplant. I'd love to know how he defines a " good molecular

response " but I'm thinking that 6 months is a bit overzealous if he's

looking for a molecular response.

It's taken many of us years to get a good molecular response and

studies have shown that molecular responses do get better after years

of treatment (that's right, I said YEARS of treatment, not months).

I'll try to dig up some papers on mutations later as right now I'm on

my way out the door. I will say though, that the nasty T315I

mutation is very rare.

Also, most doctors now feel that it would be better to go to a new

drug rather than increase the dose of Gleevec just because of the

side effect profile. Most people have difficulty tolerating the

800mg dose of Gleevec but most can tolerate the standard doses of the

new drugs which are known to be effective so why risk quality of life

issues when there are alternatives available.

More later,

Tracey

>

> From: Tracey <traceyincanada@ ...>

> Subject: [ ] Re: mutations and resistance

> groups (DOT) com

> Date: Wednesday, December 10, 2008, 2:00 PM

>

>

>

>

>

>

> Hi Kathy,

>

> Sorry for the delay in responding, it's crazy this time of year and

I

> feel as if I'm running around like the proverbial chicken with its

> head cut off.

>

> Some mutations are acquired while others are there from the

beginning

> so you're both right. You could very well have acquired one

recently

> and knowing this information will allow you to choose the right

drug

> option.

>

> If you need some journal articles supporting your case, let me know

> and I'll try to dig them up but seeing as you were seeing your

doctor

> today, I wonder if it's too late?

>

> Tracey

>

> --- In groups (DOT) com, " kathymhyland " <kathymhyland@ ...>

wrote:

> >

> > Hi, everyone. I'll be seeing a new doctor on Weds, a colleague of

> my

> > current dr, to discuss changing meds. I need some help

> understanding

> > gleevec resistance and mutations. My Dr believes I am " failing "

> > gleevec, but that we don't need to do the mutation test. She

> believes

> > that since I did well on gleevec for 3 years, I could not have a

> > mutation. I had assumed that the mutations were acquired--an

> > adaptation/evolutio nary thing. Perhaps we are both right. I

really

> > want to push for this mutation test, so any information that

would

> help

> > me plead my case is appreciated. Without a mutation present, how

> do

> > you explain gleevec " resistance? " And finally, I know each new

> drug

> > binds well to specific mutations. Without that guideline, how do

> you

> > choose which drug to use? I now she's leaning toward dasatinib.

> > Thanks for your help--have a great day!

> >

>

>

>

>

>

>

>

>

>

>

>

>

>

>

>

>

[Guest guest]

Hi Kathy,

As promised, here is a published document that discusses the issue of

mutation testing. This is the ASH paper titled " Milestones and

Monitoring in Patients with CML Treated with Imatinib " . It's

absolutely full of great info that everyone should read:

http://tinyurl.com/63ebdw

Pertinent to the mutation testing though, it says:

" Once a rise of BCR-ABL transcripts has been confirmed and compliance

ascertained, physical exam, CBC, bone marrow morphology, karyotyping,

and screening for BCR-ABL kinase domain mutations are indicated to

direct salvage therapy.

The most important piece of information is whether a patient's CML

has progressed beyond chronic phase. If so, responses to second-line

inhibitors are unlikely to last, and an allogeneic stem cell

transplant should be offered to eligible patients, using nilotinib or

dasatinib as a bridge.

Mutation analysis provides additional information. Patients with the

broadly resistant T315I mutant will not benefit from any of the

currently approved ABL inhibitors. Other mutations, while not

conferring complete resistance, influence the depth of

response......Although prospective intervention studies are not yet

available, it seems prudent to utilize this information to choose

between available kinase inhibitors. "

As you can see, transplant is only mentioned for patients who have

advanced from the chronic phase.

There's no real standard way that patients progress, some will

progress really quickly into blast phase while others will remain in

chronic phase for several years. Lottie is our chronic phase queen,

she's been in chronic phase (without a complete cytogenetic response)

for something like 13 years now and lets not forget about Skip who's

past 30 years!

Take care,

Tracey

> > >

> > > Hi, everyone. I'll be seeing a new doctor on Weds, a colleague

of

> > my

> > > current dr, to discuss changing meds. I need some help

> > understanding

> > > gleevec resistance and mutations. My Dr believes I am " failing "

> > > gleevec, but that we don't need to do the mutation test. She

> > believes

> > > that since I did well on gleevec for 3 years, I could not have

a

> > > mutation. I had assumed that the mutations were acquired--an

> > > adaptation/evolutio nary thing. Perhaps we are both right. I

> really

> > > want to push for this mutation test, so any information that

> would

> > help

> > > me plead my case is appreciated. Without a mutation present,

how

> > do

> > > you explain gleevec " resistance? " And finally, I know each new

> > drug

> > > binds well to specific mutations. Without that guideline, how

do

> > you

> > > choose which drug to use? I now she's leaning toward dasatinib.

> > > Thanks for your help--have a great day!

> > >

> >

> >

> >

> >

> >

> >

> >

> >

> >

> >

> >

> >

> >

> >

> >

> >