RE: Re: Today's Teleconference ()

[Guest guest]

Hi ,

Just some thoughts on your question. If I remember correctly

didn't lack a response to Gleevec--he had liver problems? That's

important if you are counting the number of drugs that he didn't

respond to. So far I think that is none. Another thing--Dr. Cortes

mentioned today that they have seen responses in some patients who

were on their 3rd drug. I don't think they can predict yet who will

or will not respond.

MDACC has a lot more trials than OHSU just because they are a larger

institution and trialing drugs is what they do--that may or may not

be a factor in the seemingingly different opinions?

I hesitate to mention this thought but it might be important to take

into account in any decision making--there was a young woman on the

lists a couple years ago who went to transplant because of liver

intolerance to Gleevec. She died because of liver problems in the

months following the transplant. Transplant patients have to take a

lot of drugs and some of those are bound to impact the liver.

The bottom line is I think intolerance is a different issue than non-

responsiveness. I had my annual visit at MDACC this week and I was

told by the PA that they are seeing lower side effects in some of the

newer drugs. AMN and SKI are both better tolerated than Sprycel.

She said that AMN and SKI seem to have less side effects than even

Gleevec--that's not official at this point but just her experience

with a number of patients on the different drugs. So I think

has a lot of hope from the next generation of drugs if he needs or

wants to switch at some time. He would probably need to evaluate

the specific side effect profiles of the different drugs (especially

as they relate to the liver).

Best wishes,

Dorothy

On Sep 20, 2007, at 5:34 PM, Cervera wrote:

>

> --

> There is something I do not understand. When we saw Dr. Druker he

> told us that if you dont respond to Gleevec/Sprycel, and you dont

> have a mutation, it's not like there are tons of drugs to try (most

> other drugs address mutations). This sort of suprised and I

> because everyone always talks about how many drugs there are, and

> how many are in trials, and how many " options " there are for CMl

> patients. But he seemed pretty adement that if doesnt respond

> to Sprycel, and he doesnt have a mutation, that he wouldnt keep

> trying on lots of the other drugs and would start looking for

> a bone marrow match. He said if didnt respond to Gleevec/

> Sprycel but didnt have a mutation, what would make him think that

> would respond to the second and third generation drugs?

>

> Does this make sense to you....? I am not questioning Dr. Druker,

> or you for that matter! I am just trying to get a handle on what

> the thinking is behind it...

>

> Cervera

>

>

> @...: traceyincanada@...: Thu, 20

> Sep 2007 21:27:59 +0000Subject: [ ] Re: Today's Teleconference

>

>

>

>

> It was my pleasure Lynn. I hope you see a relief soon in those side

> effects. If not, you know that there are other drugs right around

> the corner. You will always have options which is such a nice thing

> to have.Take care,Tracey> >> > Hi Everyone,> > > > In case

> any of you weren't able to listen to today's teleconference > > but

> were interested in what Dr. Cortes said, I've written a summary > >

> in two parts. This post will look at his initial " lecture " and my >

> > next post will have the question/answer period.> > > > He started

> with a brief history of CML saying that it was the first > >

> malignancy where a chromosomal change was found to cause a >

> disease. > > Past goals of CML therapy were simply to control blood

> counts but > > thanks to Gleevec and other targeted therapies, our

> goal now is to > > reach the source of the disease and allow

> patients to live long > term.> > > > Between the years of 1997-2007

> there hasn't been much of a change > in > > the number of people

> being diagnosed with CML. Prior to 1997, 2400 > > patients died a

> year from CML and now there are less than 500 > > patients dying a

> year due to CML.> > > > Survival has gone from 3-4 years prior to

> Gleevec, to now 95% of > > patients are still alive after 5 years.

> The IRIS trial has shown > us > > that more than 80% of newly

> diagnosed patients have achieved a CCR > > which has been very

> durable over 5 years. The longer the patients > > are on Gleevec,

> the lower the rates of relapse are, which is very > > encouraging.>

> > > > He said that blood levels of Imatinib (Gleevec) can predict

> the > level > > of response a patient will have. Low concentrations

> of imatinib in > > the blood, don't give patients as good of a

> response as higher > > levels. He also said that serum testing of

> Gleevec is now widely > > available.> > > > The earlier the patient

> responds, the better the outcome. Patients > > who are in CCR at 1

> year, have the best probability of a durable > > response. He

> mentioned that proper monitoring of disease is > > essential. FISH

> tests can have a false positive rate of up to 10% > so > > that

> should be taken into consideration when evaluating a patients > >

> results.> > > > A PCR test measures the patient's molecular

> response. A major > > molecular response (MMR) is a 3 log

> reduction. Each lab has a > > baseline value of what a newly

> diagnosed patient will have in terms > > of a PCR result. If for

> instance, the baseline is 50, then a one > log > > reduction would

> be 5, a two log reduction would be 0.5, and a three > > log

> reduction would be 0.05.> > > > Standard dose Imatinib has shown

> wonderful responses but higher > dose > > therapy can show faster

> and even deeper responses. He mentioned > > though that higher dose

> therapy (800mg) is still considered > > investigational, it's not

> by any means standard.> > > > Over the long term, side effects

> appear to ease up in most > patients. > > We used to be concerned

> about the long term effects of taking > Gleevec > > but after 5

> years of use, we're not so worried anymore because > people > >

> seem to be doing better and better with fewer side effects over the

> > > long term.> > > > Studies that have looked at heart problems

> have shown that Gleevec > > does not cause any more heart problems

> than you would expect to see > > in the general population.> > > >

> Dasatinib (Sprycel) is effective in all stages of disease and is >

> well > > tolerated. Cytopenias (low blood counts) are a common side

> effect > > and pleural effusions can occur in 25-30% of patients

> but it can be > > managed. Giving 100mg once daily is showing equal

> responses as the > > 70mg twice daily dose and there's less side

> effects with the 100 mg > > dose.> > > > Nilotinib (Tasigna) is

> also showing to be very effective and well > > tolerated in

> patients who are taking it in clinical trials. It has > > shown no

> pleural effusions but can sometimes cause liver enzymes to > >

> rise.> > > > We continue to be excited about CML therapy as more

> hopeful drugs > are > > on the horizon. SKI-606 and INNO-406 are

> showing encouraging > > responses in trials so far.> > > > With so

> many drugs to chose from, there will soon be a question as > to > >

> how to select a drug to use. Side effects should be considered >

> when > > choosing a drug. Various mutations are better targeted

> with some > > drugs over others so that's another consideration to

> look at.> > > > 40%-60% of patients who fail imatinib have a

> mutation but most of > > those mutations can be managed with one of

> the other second or > third > > generation drugs. MK-0457 is

> showing activity against the more > > serious T315I mutation, which

> is encouraging.> > > > We want to eliminate the last leukemia cell,

> the " mother cell " so > > that we can cure CML. We have had a

> significant amount of success > in > > treating CML but we still

> have a way to go to cure it. We are > > hopeful for a cure in the

> " very near future " .> > > > Clinical trials are essential for

> gaining knowledge so it's > > important that patients continue to

> participate in trials if they > > can.> > > > Advances in CML have

> been very quick. We now have 3 generations of > > inhibitors to

> chose from.> >>

>

>

>

>

>

>

> _________________________________________________________________

> More photos; more messages; more whatever – Get MORE with Windows

> Live™ Hotmail®. NOW with 5GB storage.

> http://imagine-windowslive.com/hotmail/?locale=en-

> us & ocid=TXT_TAGHM_migration_HM_mini_5G_0907

>

>

[Guest guest]

Thanks Dorothy! Yes, we definitely know and realize that 's liver

intolerance in no way meant that he didnt " RESPOND " to Gleevec. In fact, that

was the main " oops " we've had so far--the fact that his onc did not do a PCR or

a BMB BEFORE taking him off Gleevec. It immediately made sense when Dr. Druker

pointed that out to us... " ...well, you went off Gleevec due to liver problems,

but since no testing was done, we dont actually know how well you were

responding to it. " As soon as he said it, we realized.... " OOPS " . So, without

that knowledge as to whether or not was, in fact, responding to Gleevec,

felt " let down " . Only in that if he WAS responding well to it, chances are

he would respond well to Sprycel, and he wouldnt have to even wonder " what if? " .

But we dont know...and we wont know for another little while here. has

since eased into the not knowing....we dont think about the upcoming tests, and

just are thankful for how great feels...he really says " I feel normal " .

!!

@...: doemery@...: Thu, 20 Sep 2007 19:14:47

-0400Subject: Re: [ ] Re: Today's Teleconference ()

Hi ,Just some thoughts on your question. If I remember correctly

didn't lack a response to Gleevec--he had liver problems? That's important if

you are counting the number of drugs that he didn't respond to. So far I think

that is none. Another thing--Dr. Cortes mentioned today that they have seen

responses in some patients who were on their 3rd drug. I don't think they can

predict yet who will or will not respond.MDACC has a lot more trials than OHSU

just because they are a larger institution and trialing drugs is what they

do--that may or may not be a factor in the seemingingly different opinions?I

hesitate to mention this thought but it might be important to take into account

in any decision making--there was a young woman on the lists a couple years ago

who went to transplant because of liver intolerance to Gleevec. She died because

of liver problems in the months following the transplant. Transplant patients

have to take a lot of drugs and some of those are bound to impact the liver.The

bottom line is I think intolerance is a different issue than non-

responsiveness. I had my annual visit at MDACC this week and I was told by the

PA that they are seeing lower side effects in some of the newer drugs. AMN and

SKI are both better tolerated than Sprycel. She said that AMN and SKI seem to

have less side effects than even Gleevec--that's not official at this point but

just her experience with a number of patients on the different drugs. So I think

has a lot of hope from the next generation of drugs if he needs or wants to

switch at some time. He would probably need to evaluate the specific side effect

profiles of the different drugs (especially as they relate to the liver).Best

wishes,DorothyOn Sep 20, 2007, at 5:34 PM, Cervera wrote:>> --> There

is something I do not understand. When we saw Dr. Druker he > told us that if

you dont respond to Gleevec/Sprycel, and you dont > have a mutation, it's not

like there are tons of drugs to try (most > other drugs address mutations). This

sort of suprised and I > because everyone always talks about how many drugs

there are, and > how many are in trials, and how many " options " there are for

CMl > patients. But he seemed pretty adement that if doesnt respond > to

Sprycel, and he doesnt have a mutation, that he wouldnt keep > trying on

lots of the other drugs and would start looking for > a bone marrow match. He

said if didnt respond to Gleevec/ > Sprycel but didnt have a mutation, what

would make him think that > would respond to the second and third

generation drugs?>> Does this make sense to you....? I am not questioning Dr.

Druker, > or you for that matter! I am just trying to get a handle on what > the

thinking is behind it...>> Cervera>>> @...:

traceyincanada@...: Thu, 20 > Sep 2007 21:27:59 +0000Subject: [ ]

Re: Today's Teleconference>>>>> It was my pleasure Lynn. I hope you see a relief

soon in those side > effects. If not, you know that there are other drugs right

around > the corner. You will always have options which is such a nice thing >

to have.Take care,Tracey> >> > Hi Everyone,> > > > In case > any of you

weren't able to listen to today's teleconference > > but > were interested in

what Dr. Cortes said, I've written a summary > > > in two parts. This post will

look at his initial " lecture " and my > > > next post will have the

question/answer period.> > > > He started > with a brief history of CML saying

that it was the first > > > malignancy where a chromosomal change was found to

cause a > > disease. > > Past goals of CML therapy were simply to control blood

> counts but > > thanks to Gleevec and other targeted therapies, our > goal now

is to > > reach the source of the disease and allow > patients to live long >

term.> > > > Between the years of 1997-2007 > there hasn't been much of a change

> in > > the number of people > being diagnosed with CML. Prior to 1997, 2400 >

> patients died a > year from CML and now there are less than 500 > > patients

dying a > year due to CML.> > > > Survival has gone from 3-4 years prior to >

Gleevec, to now 95% of > > patients are still alive after 5 years. > The IRIS

trial has shown > us > > that more than 80% of newly > diagnosed patients have

achieved a CCR > > which has been very > durable over 5 years. The longer the

patients > > are on Gleevec, > the lower the rates of relapse are, which is very

> > encouraging.> > > > > He said that blood levels of Imatinib (Gleevec) can

predict > the > level > > of response a patient will have. Low concentrations >

of imatinib in > > the blood, don't give patients as good of a > response as

higher > > levels. He also said that serum testing of > Gleevec is now widely >

> available.> > > > The earlier the patient > responds, the better the outcome.

Patients > > who are in CCR at 1 > year, have the best probability of a durable

> > response. He > mentioned that proper monitoring of disease is > > essential.

FISH > tests can have a false positive rate of up to 10% > so > > that > should

be taken into consideration when evaluating a patients > > > results.> > > > A

PCR test measures the patient's molecular > response. A major > > molecular

response (MMR) is a 3 log > reduction. Each lab has a > > baseline value of what

a newly > diagnosed patient will have in terms > > of a PCR result. If for >

instance, the baseline is 50, then a one > log > > reduction would > be 5, a two

log reduction would be 0.5, and a three > > log > reduction would be 0.05.> > >

> Standard dose Imatinib has shown > wonderful responses but higher > dose > >

therapy can show faster > and even deeper responses. He mentioned > > though

that higher dose > therapy (800mg) is still considered > > investigational, it's

not > by any means standard.> > > > Over the long term, side effects > appear to

ease up in most > patients. > > We used to be concerned > about the long term

effects of taking > Gleevec > > but after 5 > years of use, we're not so worried

anymore because > people > > > seem to be doing better and better with fewer

side effects over the > > > long term.> > > > Studies that have looked at heart

problems > have shown that Gleevec > > does not cause any more heart problems >

than you would expect to see > > in the general population.> > > > > Dasatinib

(Sprycel) is effective in all stages of disease and is > > well > > tolerated.

Cytopenias (low blood counts) are a common side > effect > > and pleural

effusions can occur in 25-30% of patients > but it can be > > managed. Giving

100mg once daily is showing equal > responses as the > > 70mg twice daily dose

and there's less side > effects with the 100 mg > > dose.> > > > Nilotinib

(Tasigna) is > also showing to be very effective and well > > tolerated in >

patients who are taking it in clinical trials. It has > > shown no > pleural

effusions but can sometimes cause liver enzymes to > > > rise.> > > > We

continue to be excited about CML therapy as more > hopeful drugs > are > > on

the horizon. SKI-606 and INNO-406 are > showing encouraging > > responses in

trials so far.> > > > With so > many drugs to chose from, there will soon be a

question as > to > > > how to select a drug to use. Side effects should be

considered > > when > > choosing a drug. Various mutations are better targeted >

with some > > drugs over others so that's another consideration to > look at.> >

> > 40%-60% of patients who fail imatinib have a > mutation but most of > >

those mutations can be managed with one of > the other second or > third > >

generation drugs. MK-0457 is > showing activity against the more > > serious

T315I mutation, which > is encouraging.> > > > We want to eliminate the last

leukemia cell, > the " mother cell " so > > that we can cure CML. We have had a >

significant amount of success > in > > treating CML but we still > have a way to

go to cure it. We are > > hopeful for a cure in the > " very near future " .> > > >

Clinical trials are essential for > gaining knowledge so it's > > important that

patients continue to > participate in trials if they > > can.> > > > Advances in

CML have > been very quick. We now have 3 generations of > > inhibitors to >

chose from.> >>>>>>>>>

__________________________________________________________> More photos; more

messages; more whatever – Get MORE with Windows > Live™ Hotmail®. NOW with 5GB

storage.> http://imagine-windowslive.com/hotmail/?locale=en- >

us & ocid=TXT_TAGHM_migration_HM_mini_5G_0907>> [Non-text portions of this message

have been removed]>>>>>