RE: Gleevec still the winner

[Guest guest]

Patients with CML need all the arsenal at their disposal to have a fighting

chance to beat CML back. Calling one treatment versus another " winner " is

immature at best especially to those who did fail with Gleevec. Let's keep

politics out of CML treatment. The only thing we should all strive for is that

every single CML patient reaches and keeps permanent pcru with whatever

treatment that works! And is that is Gleevec, fine; if it is another treatment

that is equally fine.

Novartis deserves our accolades for being the first successful treatment.

Period.

[ ] Gleevec still the winner

Gleevec is still the winner in treating CML. Dr. Cortes wonders what would be

needed to dethrone imatinib as the standard of care for patients with newly

diagnosed CML. He points out that although we would ultimately like to improve

survival, it is unrealistic to expect an improvement in the short term, given

the excellent survival at 5 years for patients treated with imatinib. " Improving

survival free from transformation is similarly difficult, " he writes. However,

an improvement in event-free survival would be valuable and is a more reachable

goal, particularly if a broader definition of " event free " is used, such as the

one suggested by the authors of the current study, which includes toxicity and

failure to achieve (or loss of) major cytogenetic remission (MCyR) or CCyR.

Most of the available data on imatinib efficacy in newly diagnosed CML patients

is drawn from the International Randomized Study of Interferon (IRIS), which was

conducted under the supervision of the manufacturer. Most patients achieved a

durable CCyR, with an estimated overall survival of 89% at 5 years, but 20% of

patients were censored for various reasons, and event-free survival and

progression to accelerated or blastic phase were only evaluated for patients who

continued to use imatinib.

Comparison with IRIS

Hugues de Lavallade, MD, and colleagues from Hammersmith Hospital and Imperial

College, in London, United Kingdom, performed a single-center trial that

evaluated the efficacy of imatinib in 204 consecutive adult patients with newly

diagnosed BCR-ABL-positive CML in the chronic phase who were treated from June

2000 until August 2006. The primary goal of their study was to see whether

overall results differed from those obtained from an analysis performed on an

intention-to-treat basis where all events were recorded. All patients received

imatinib as first-line therapy; it was started within 6 months of their

diagnosis. The researchers evaluated hematologic, cytogenetic, and molecular

response, and progression-free and overall survival.

Even though the median follow-up of 38 months in their study was shorter than

that in the IRIS study, the results were similar. In the IRIS trial, the

cumulative incidence of CCyR at 60 months was 87%, event-free survival was 83%,

and overall survival was 89%. In the current study, the rates were 82.7%, 81.3%,

and 83.2%, respectively. After a median of 15.5 months, 54 patients (26%) had

permanently discontinued imatinib, for reasons that included adverse events,

loss of complete hematologic response, progression to accelerated or blastic

phase, and loss of MCyR. The dose of imatinib was increased in 75 patients (37%)

during the study period.

Kinase domain (KD) mutations have been associated with an acquired resistance to

tyrosine kinase inhibitors and, during follow-up, 12 different KD mutations were

detected in 11 patients. The development of KD mutations was significant for

predicting loss of CCyR, but not for predicting loss of a complete hematologic

response, progression-free survival, or overall survival. The researchers also

noted that the major predictor for both overall and progression-free survival

was a cytogenetic response at 1 year, which has been reported previously. " It is

difficult to define imatinib failure, in part because some patients achieve

hematologic response rapidly but take substantial time to achieve a CCyR, " write

the authors. " However, it may be inappropriate to wait indefinitely for a CCyR. "

They point out that in the IRIS study, patients who did not achieve a MCyR but

who discontinued imatinib before loss of a complete hematologic response were

not considered to have failed imatinib therapy. In addition, patients who

stopped treatment because of adverse effects were censored. " Consequently,

event-free survival, as defined in the IRIS study, is likely to be an

overestimate, " they write. " When these failures are considered appropriately, as

in an intention-to-treat analysis, the real response rate to imatinib at 5 years

is 62.7%. "

The study was supported by the Health Research Biomedical Research Centre

Funding Scheme and a grant from the " Fondation de France " The authors have

disclosed no relevant financial relationships.

Entire article can be read at this website:

http://www.medscape.com/viewarticle/577662

<http://www.medscape.com/viewarticle/577662>

Blessings,

Lottie

[Guest guest]

 

 

I am nearly 100% sure Lottie was not  bringing politics into this forum.  My

take is that she is passing the news on that Gleevec remains a great approach

for many long term and most new CML patients.   I have been on it for nearly 6

years now and I am PRCU (dependant on which lab).  I was CCR in 4 months.   

Lottie digs into the details available on the World Wide Net and shares it

here.  Most of what she shares is very encouraging.

 

Gleevec is a winner!  The second wave of drugs are too!  I agree with you!! we

need them all in the arsenal to keep the runway of our lives clear and

promising.   We need to encourage, praise and thank all the Drs and Scientists

and Team members for their on going work to continue to build new tools for

fighting and maybe someday eliminating CML!

 

 

Love and Mercy!

 

 

Chris

From: Rutigliano, <_Rutigliano@...>

Subject: RE: [ ] Gleevec still the winner

" " < >

Date: Friday, April 24, 2009, 9:21 AM

Patients with CML need all the arsenal at their disposal to have a fighting

chance to beat CML back. Calling one treatment versus another " winner " is

immature at best especially to those who did fail with Gleevec. Let's keep

politics out of CML treatment. The only thing we should all strive for is that

every single CML patient reaches and keeps permanent pcru with whatever

treatment that works! And is that is Gleevec, fine; if it is another treatment

that is equally fine.

Novartis deserves our accolades for being the first successful treatment.

Period.

[ ] Gleevec still the winner

Gleevec is still the winner in treating CML. Dr. Cortes wonders what would be

needed to dethrone imatinib as the standard of care for patients with newly

diagnosed CML. He points out that although we would ultimately like to improve

survival, it is unrealistic to expect an improvement in the short term, given

the excellent survival at 5 years for patients treated with imatinib. " Improving

survival free from transformation is similarly difficult, " he writes. However,

an improvement in event-free survival would be valuable and is a more reachable

goal, particularly if a broader definition of " event free " is used, such as the

one suggested by the authors of the current study, which includes toxicity and

failure to achieve (or loss of) major cytogenetic remission (MCyR) or CCyR.

Most of the available data on imatinib efficacy in newly diagnosed CML patients

is drawn from the International Randomized Study of Interferon (IRIS), which was

conducted under the supervision of the manufacturer. Most patients achieved a

durable CCyR, with an estimated overall survival of 89% at 5 years, but 20% of

patients were censored for various reasons, and event-free survival and

progression to accelerated or blastic phase were only evaluated for patients who

continued to use imatinib.

Comparison with IRIS

Hugues de Lavallade, MD, and colleagues from Hammersmith Hospital and Imperial

College, in London, United Kingdom, performed a single-center trial that

evaluated the efficacy of imatinib in 204 consecutive adult patients with newly

diagnosed BCR-ABL-positive CML in the chronic phase who were treated from June

2000 until August 2006. The primary goal of their study was to see whether

overall results differed from those obtained from an analysis performed on an

intention-to- treat basis where all events were recorded. All patients received

imatinib as first-line therapy; it was started within 6 months of their

diagnosis. The researchers evaluated hematologic, cytogenetic, and molecular

response, and progression- free and overall survival.

Even though the median follow-up of 38 months in their study was shorter than

that in the IRIS study, the results were similar. In the IRIS trial, the

cumulative incidence of CCyR at 60 months was 87%, event-free survival was 83%,

and overall survival was 89%. In the current study, the rates were 82.7%, 81.3%,

and 83.2%, respectively. After a median of 15.5 months, 54 patients (26%) had

permanently discontinued imatinib, for reasons that included adverse events,

loss of complete hematologic response, progression to accelerated or blastic

phase, and loss of MCyR. The dose of imatinib was increased in 75 patients (37%)

during the study period.

Kinase domain (KD) mutations have been associated with an acquired resistance to

tyrosine kinase inhibitors and, during follow-up, 12 different KD mutations were

detected in 11 patients. The development of KD mutations was significant for

predicting loss of CCyR, but not for predicting loss of a complete hematologic

response, progression- free survival, or overall survival. The researchers also

noted that the major predictor for both overall and progression- free survival

was a cytogenetic response at 1 year, which has been reported previously. " It is

difficult to define imatinib failure, in part because some patients achieve

hematologic response rapidly but take substantial time to achieve a CCyR, " write

the authors. " However, it may be inappropriate to wait indefinitely for a CCyR. "

They point out that in the IRIS study, patients who did not achieve a MCyR but

who discontinued imatinib before loss of a complete hematologic response were

not considered to have failed imatinib therapy. In addition, patients who

stopped treatment because of adverse effects were censored. " Consequently,

event-free survival, as defined in the IRIS study, is likely to be an

overestimate, " they write. " When these failures are considered appropriately,

as in an intention-to- treat analysis, the real response rate to imatinib at 5

years is 62.7%. "

The study was supported by the Health Research Biomedical Research Centre

Funding Scheme and a grant from the " Fondation de France " The authors have

disclosed no relevant financial relationships.

Entire article can be read at this website:

http://www.medscape .com/viewarticle /577662 <http://www.medscape

..com/viewarticle /577662>

Blessings,

Lottie

[Guest guest]

Brothers and Sisters,

 

 I don't think the idea was Gleevec is the winner and all others are losers. It

is not a matter of competition between therapies. Death does not recognize

politics and who knows that better than our Lottie. , my CML family member,

I think you may have misunderstood.

 

Many of us on this list are taking different therapies but we all there for each

other. For all of us on the gold there is a great possibility that we will

develop mutations or need to try the second , third etc generation drugs due to

side effects. We are happy that new therapies continue to be developed.Gleevec

is first generation and has the most research behind it.  So I think  Dr.

Cortes  felt safe in saying statistically- we have a winner. So often drugs

appear to be the answer and then as time goes on side effects or long term

effectiveness may show it to not be as promising as first believed. I think

Gleevec has about 10 years of research behind it and although it isn't the cure,

it has changed the face of survival.  Hopefully, the other drugs will continue

to improve our survival rates. I think we are all grateful for whatever keeps us

alive and the hope that each new generation of drugs brings.They say it takes a

village to raise a child

but it will take many kinds of treatments to keep all of us alive and

thriving-no one knows it better than our long time warriors like Lottie, Zavie,

Bobby etc who  endured Interferon and entered clinical trials when Gleevec was

known with letters and numbers. 

 

We share the same fight. Wishing you all health and continued hope.

 

Chi

  

 

From: Rutigliano, <_Rutigliano@ adp.com>

Subject: RE: [ ] Gleevec still the winner

" groups (DOT) com " <groups (DOT) com>

Date: Friday, April 24, 2009, 9:21 AM

Patients with CML need all the arsenal at their disposal to have a fighting

chance to beat CML back. Calling one treatment versus another " winner " is

immature at best especially to those who did fail with Gleevec. Let's keep

politics out of CML treatment. The only thing we should all strive for is that

every single CML patient reaches and keeps permanent pcru with whatever

treatment that works! And is that is Gleevec, fine; if it is another treatment

that is equally fine.

Novartis deserves our accolades for being the first successful treatment.

Period.

[ ] Gleevec still the winner

Gleevec is still the winner in treating CML. Dr. Cortes wonders what would be

needed to dethrone imatinib as the standard of care for patients with newly

diagnosed CML. He points out that although we would ultimately like to improve

survival, it is unrealistic to expect an improvement in the short term, given

the excellent survival at 5 years for patients treated with imatinib. " Improving

survival free from transformation is similarly difficult, " he writes. However,

an improvement in event-free survival would be valuable and is a more reachable

goal, particularly if a broader definition of " event free " is used, such as the

one suggested by the authors of the current study, which includes toxicity and

failure to achieve (or loss of) major cytogenetic remission (MCyR) or CCyR.

Most of the available data on imatinib efficacy in newly diagnosed CML patients

is drawn from the International Randomized Study of Interferon (IRIS), which was

conducted under the supervision of the manufacturer. Most patients achieved a

durable CCyR, with an estimated overall survival of 89% at 5 years, but 20% of

patients were censored for various reasons, and event-free survival and

progression to accelerated or blastic phase were only evaluated for patients who

continued to use imatinib.

Comparison with IRIS

Hugues de Lavallade, MD, and colleagues from Hammersmith Hospital and Imperial

College, in London, United Kingdom, performed a single-center trial that

evaluated the efficacy of imatinib in 204 consecutive adult patients with newly

diagnosed BCR-ABL-positive CML in the chronic phase who were treated from June

2000 until August 2006. The primary goal of their study was to see whether

overall results differed from those obtained from an analysis performed on an

intention-to- treat basis where all events were recorded. All patients received

imatinib as first-line therapy; it was started within 6 months of their

diagnosis. The researchers evaluated hematologic, cytogenetic, and molecular

response, and progression- free and overall survival.

Even though the median follow-up of 38 months in their study was shorter than

that in the IRIS study, the results were similar. In the IRIS trial, the

cumulative incidence of CCyR at 60 months was 87%, event-free survival was 83%,

and overall survival was 89%. In the current study, the rates were 82.7%, 81.3%,

and 83.2%, respectively. After a median of 15.5 months, 54 patients (26%) had

permanently discontinued imatinib, for reasons that included adverse events,

loss of complete hematologic response, progression to accelerated or blastic

phase, and loss of MCyR. The dose of imatinib was increased in 75 patients (37%)

during the study period.

Kinase domain (KD) mutations have been associated with an acquired resistance to

tyrosine kinase inhibitors and, during follow-up, 12 different KD mutations were

detected in 11 patients. The development of KD mutations was significant for

predicting loss of CCyR, but not for predicting loss of a complete hematologic

response, progression- free survival, or overall survival. The researchers also

noted that the major predictor for both overall and progression- free survival

was a cytogenetic response at 1 year, which has been reported previously. " It is

difficult to define imatinib failure, in part because some patients achieve

hematologic response rapidly but take substantial time to achieve a CCyR, " write

the authors. " However, it may be inappropriate to wait indefinitely for a CCyR. "

They point out that in the IRIS study, patients who did not achieve a MCyR but

who discontinued imatinib before loss of a complete hematologic response were

not considered to have failed imatinib therapy. In addition, patients who

stopped treatment because of adverse effects were censored. " Consequently,

event-free survival, as defined in the IRIS study, is likely to be an

overestimate, " they write. " When these failures are considered appropriately,

as in an intention-to- treat analysis, the real response rate to imatinib at 5

years is 62.7%. "

The study was supported by the Health Research Biomedical Research Centre

Funding Scheme and a grant from the " Fondation de France " The authors have

disclosed no relevant financial relationships.

Entire article can be read at this website:

http://www.medscape .com/viewarticle /577662 <http://www.medscape

..com/viewarticle /577662>

Blessings,

Lottie

[Guest guest]

Hi Chi,

I totally agree - Glivec will always be the first line standard due to the

depth of research behind. Certainly here in Australia that will be the case

for years to come. I am grateful for the 2nd and 3rd line therapies and we

are so lucky to have them to fall back on. Especially for those of us on

Tasigna, there is very little statistical data gathered as to the long term

outlook.

Regards,

from Down Under

From: [mailto: ] On Behalf Of china

neal

Sent: Saturday, 25 April 2009 3:49 AM

Subject: RE: [ ] Gleevec still the winner

Brothers and Sisters,

I don't think the idea was Gleevec is the winner and all others are losers.

It is not a matter of competition between therapies. Death does not

recognize politics and who knows that better than our Lottie. , my CML

family member, I think you may have misunderstood.

Many of us on this list are taking different therapies but we all there for

each other. For all of us on the gold there is a great possibility that we

will develop mutations or need to try the second , third etc generation

drugs due to side effects. We are happy that new therapies continue to be

developed.Gleevec is first generation and has the most research behind it.

So I think Dr. Cortes felt safe in saying statistically- we have a winner.

So often drugs appear to be the answer and then as time goes on side effects

or long term effectiveness may show it to not be as promising as first

believed. I think Gleevec has about 10 years of research behind it and

although it isn't the cure, it has changed the face of survival. Hopefully,

the other drugs will continue to improve our survival rates. I think we are

all grateful for whatever keeps us alive and the hope that each new

generation of drugs brings.They say it takes a village to raise a child

but it will take many kinds of treatments to keep all of us alive and

thriving-no one knows it better than our long time warriors like Lottie,

Zavie, Bobby etc who endured Interferon and entered clinical trials when

Gleevec was known with letters and numbers.

We share the same fight. Wishing you all health and continued hope.

Chi

From: Rutigliano, <_Rutigliano@ adp.com>

Subject: RE: [ ] Gleevec still the winner

" groups (DOT) com " <groups (DOT) com>

Date: Friday, April 24, 2009, 9:21 AM

Patients with CML need all the arsenal at their disposal to have a fighting

chance to beat CML back. Calling one treatment versus another " winner " is

immature at best especially to those who did fail with Gleevec. Let's keep

politics out of CML treatment. The only thing we should all strive for is

that every single CML patient reaches and keeps permanent pcru with whatever

treatment that works! And is that is Gleevec, fine; if it is another

treatment that is equally fine.

Novartis deserves our accolades for being the first successful treatment.

Period.

[ ] Gleevec still the winner

Gleevec is still the winner in treating CML. Dr. Cortes wonders what would

be needed to dethrone imatinib as the standard of care for patients with

newly diagnosed CML. He points out that although we would ultimately like to

improve survival, it is unrealistic to expect an improvement in the short

term, given the excellent survival at 5 years for patients treated with

imatinib. " Improving survival free from transformation is similarly

difficult, " he writes. However, an improvement in event-free survival would

be valuable and is a more reachable goal, particularly if a broader

definition of " event free " is used, such as the one suggested by the authors

of the current study, which includes toxicity and failure to achieve (or

loss of) major cytogenetic remission (MCyR) or CCyR.

Most of the available data on imatinib efficacy in newly diagnosed CML

patients is drawn from the International Randomized Study of Interferon

(IRIS), which was conducted under the supervision of the manufacturer. Most

patients achieved a durable CCyR, with an estimated overall survival of 89%

at 5 years, but 20% of patients were censored for various reasons, and

event-free survival and progression to accelerated or blastic phase were

only evaluated for patients who continued to use imatinib.

Comparison with IRIS

Hugues de Lavallade, MD, and colleagues from Hammersmith Hospital and

Imperial College, in London, United Kingdom, performed a single-center trial

that evaluated the efficacy of imatinib in 204 consecutive adult patients

with newly diagnosed BCR-ABL-positive CML in the chronic phase who were

treated from June 2000 until August 2006. The primary goal of their study

was to see whether overall results differed from those obtained from an

analysis performed on an intention-to- treat basis where all events were

recorded. All patients received imatinib as first-line therapy; it was

started within 6 months of their diagnosis. The researchers evaluated

hematologic, cytogenetic, and molecular response, and progression- free and

overall survival.

Even though the median follow-up of 38 months in their study was shorter

than that in the IRIS study, the results were similar. In the IRIS trial,

the cumulative incidence of CCyR at 60 months was 87%, event-free survival

was 83%, and overall survival was 89%. In the current study, the rates were

82.7%, 81.3%, and 83.2%, respectively. After a median of 15.5 months, 54

patients (26%) had permanently discontinued imatinib, for reasons that

included adverse events, loss of complete hematologic response, progression

to accelerated or blastic phase, and loss of MCyR. The dose of imatinib was

increased in 75 patients (37%) during the study period.

Kinase domain (KD) mutations have been associated with an acquired

resistance to tyrosine kinase inhibitors and, during follow-up, 12 different

KD mutations were detected in 11 patients. The development of KD mutations

was significant for predicting loss of CCyR, but not for predicting loss of

a complete hematologic response, progression- free survival, or overall

survival. The researchers also noted that the major predictor for both

overall and progression- free survival was a cytogenetic response at 1 year,

which has been reported previously. " It is difficult to define imatinib

failure, in part because some patients achieve hematologic response rapidly

but take substantial time to achieve a CCyR, " write the authors. " However,

it may be inappropriate to wait indefinitely for a CCyR. "

They point out that in the IRIS study, patients who did not achieve a MCyR

but who discontinued imatinib before loss of a complete hematologic response

were not considered to have failed imatinib therapy. In addition, patients

who stopped treatment because of adverse effects were censored.

" Consequently, event-free survival, as defined in the IRIS study, is likely

to be an overestimate, " they write. " When these failures are considered

appropriately, as in an intention-to- treat analysis, the real response rate

to imatinib at 5 years is 62.7%. "

The study was supported by the Health Research Biomedical Research Centre

Funding Scheme and a grant from the " Fondation de France " The authors have

disclosed no relevant financial relationships.

Entire article can be read at this website:

http://www.medscape .com/viewarticle /577662 <http://www.medscape

..com/viewarticle /577662>

Blessings,

Lottie

[Guest guest]

Dear ,

I think implying Lottie, an 80 year old hellcat, immature is immature. There

wasn't any " politics " in Lottie's naming Gleevec a winner. The stuff didn't

even work for her. She was merely citing Dr. Cortes, a CML expert. I'm quite

sure Lottie wishes she could find a treatment that would beat the beast, even if

that treatment involved standing on her head and rubbing her tummy.

Bob , Granger, Indiana

A 12 Year CML veteran

>

> Patients with CML need all the arsenal at their disposal to have a fighting

chance to beat CML back. Calling one treatment versus another " winner " is

immature at best especially to those who did fail with Gleevec. Let's keep

politics out of CML treatment. The only thing we should all strive for is that

every single CML patient reaches and keeps permanent pcru with whatever

treatment that works! And is that is Gleevec, fine; if it is another treatment

that is equally fine.

> Novartis deserves our accolades for being the first successful treatment.

Period.

>

> [ ] Gleevec still the winner

>

>

>

> Gleevec is still the winner in treating CML. Dr. Cortes wonders what would be

needed to dethrone imatinib as the standard of care for patients with newly

diagnosed CML. He points out that although we would ultimately like to improve

survival, it is unrealistic to expect an improvement in the short term, given

the excellent survival at 5 years for patients treated with imatinib. " Improving

survival free from transformation is similarly difficult, " he writes. However,

an improvement in event-free survival would be valuable and is a more reachable

goal, particularly if a broader definition of " event free " is used, such as the

one suggested by the authors of the current study, which includes toxicity and

failure to achieve (or loss of) major cytogenetic remission (MCyR) or CCyR.

>

> Most of the available data on imatinib efficacy in newly diagnosed CML

patients is drawn from the International Randomized Study of Interferon (IRIS),

which was conducted under the supervision of the manufacturer. Most patients

achieved a durable CCyR, with an estimated overall survival of 89% at 5 years,

but 20% of patients were censored for various reasons, and event-free survival

and progression to accelerated or blastic phase were only evaluated for patients

who continued to use imatinib.

>

> Comparison with IRIS

>

> Hugues de Lavallade, MD, and colleagues from Hammersmith Hospital and Imperial

College, in London, United Kingdom, performed a single-center trial that

evaluated the efficacy of imatinib in 204 consecutive adult patients with newly

diagnosed BCR-ABL-positive CML in the chronic phase who were treated from June

2000 until August 2006. The primary goal of their study was to see whether

overall results differed from those obtained from an analysis performed on an

intention-to-treat basis where all events were recorded. All patients received

imatinib as first-line therapy; it was started within 6 months of their

diagnosis. The researchers evaluated hematologic, cytogenetic, and molecular

response, and progression-free and overall survival.

>

> Even though the median follow-up of 38 months in their study was shorter than

that in the IRIS study, the results were similar. In the IRIS trial, the

cumulative incidence of CCyR at 60 months was 87%, event-free survival was 83%,

and overall survival was 89%. In the current study, the rates were 82.7%, 81.3%,

and 83.2%, respectively. After a median of 15.5 months, 54 patients (26%) had

permanently discontinued imatinib, for reasons that included adverse events,

loss of complete hematologic response, progression to accelerated or blastic

phase, and loss of MCyR. The dose of imatinib was increased in 75 patients (37%)

during the study period.

>

> Kinase domain (KD) mutations have been associated with an acquired resistance

to tyrosine kinase inhibitors and, during follow-up, 12 different KD mutations

were detected in 11 patients. The development of KD mutations was significant

for predicting loss of CCyR, but not for predicting loss of a complete

hematologic response, progression-free survival, or overall survival. The

researchers also noted that the major predictor for both overall and

progression-free survival was a cytogenetic response at 1 year, which has been

reported previously. " It is difficult to define imatinib failure, in part because

some patients achieve hematologic response rapidly but take substantial time to

achieve a CCyR, " write the authors. " However, it may be inappropriate to wait

indefinitely for a CCyR. "

>

> They point out that in the IRIS study, patients who did not achieve a MCyR but

who discontinued imatinib before loss of a complete hematologic response were

not considered to have failed imatinib therapy. In addition, patients who

stopped treatment because of adverse effects were censored. " Consequently,

event-free survival, as defined in the IRIS study, is likely to be an

overestimate, " they write. " When these failures are considered appropriately, as

in an intention-to-treat analysis, the real response rate to imatinib at 5 years

is 62.7%. "

>

> The study was supported by the Health Research Biomedical Research Centre

Funding Scheme and a grant from the " Fondation de France " The authors have

disclosed no relevant financial relationships.

>

> Entire article can be read at this website:

>

> http://www.medscape.com/viewarticle/577662

<http://www.medscape.com/viewarticle/577662>

>

> Blessings,

>

> Lottie

>

>

[Guest guest]

Standing on your head and rubbing your tummy!!! Lottie I'm in. I think we

should take pictures. Whatever works

Luv Eva

From:

Sent: Saturday, April 25, 2009 10:14 AM

Subject: Re: [ ] Gleevec still the winner

Dear ,

I think implying Lottie, an 80 year old hellcat, immature is immature. There

wasn't any " politics " in Lottie's naming Gleevec a winner. The stuff didn't even

work for her. She was merely citing Dr. Cortes, a CML expert. I'm quite sure

Lottie wishes she could find a treatment that would beat the beast, even if that

treatment involved standing on her head and rubbing her tummy.

Bob , Granger, Indiana

A 12 Year CML veteran

>

> Patients with CML need all the arsenal at their disposal to have a fighting

chance to beat CML back. Calling one treatment versus another " winner " is

immature at best especially to those who did fail with Gleevec. Let's keep

politics out of CML treatment. The only thing we should all strive for is that

every single CML patient reaches and keeps permanent pcru with whatever

treatment that works! And is that is Gleevec, fine; if it is another treatment

that is equally fine.

> Novartis deserves our accolades for being the first successful treatment.

Period.

>

> [ ] Gleevec still the winner

>

>

>

> Gleevec is still the winner in treating CML. Dr. Cortes wonders what would be

needed to dethrone imatinib as the standard of care for patients with newly

diagnosed CML. He points out that although we would ultimately like to improve

survival, it is unrealistic to expect an improvement in the short term, given

the excellent survival at 5 years for patients treated with imatinib. " Improving

survival free from transformation is similarly difficult, " he writes. However,

an improvement in event-free survival would be valuable and is a more reachable

goal, particularly if a broader definition of " event free " is used, such as the

one suggested by the authors of the current study, which includes toxicity and

failure to achieve (or loss of) major cytogenetic remission (MCyR) or CCyR.

>

> Most of the available data on imatinib efficacy in newly diagnosed CML

patients is drawn from the International Randomized Study of Interferon (IRIS),

which was conducted under the supervision of the manufacturer. Most patients

achieved a durable CCyR, with an estimated overall survival of 89% at 5 years,

but 20% of patients were censored for various reasons, and event-free survival

and progression to accelerated or blastic phase were only evaluated for patients

who continued to use imatinib.

>

> Comparison with IRIS

>

> Hugues de Lavallade, MD, and colleagues from Hammersmith Hospital and Imperial

College, in London, United Kingdom, performed a single-center trial that

evaluated the efficacy of imatinib in 204 consecutive adult patients with newly

diagnosed BCR-ABL-positive CML in the chronic phase who were treated from June

2000 until August 2006. The primary goal of their study was to see whether

overall results differed from those obtained from an analysis performed on an

intention-to-treat basis where all events were recorded. All patients received

imatinib as first-line therapy; it was started within 6 months of their

diagnosis. The researchers evaluated hematologic, cytogenetic, and molecular

response, and progression-free and overall survival.

>

> Even though the median follow-up of 38 months in their study was shorter than

that in the IRIS study, the results were similar. In the IRIS trial, the

cumulative incidence of CCyR at 60 months was 87%, event-free survival was 83%,

and overall survival was 89%. In the current study, the rates were 82.7%, 81.3%,

and 83.2%, respectively. After a median of 15.5 months, 54 patients (26%) had

permanently discontinued imatinib, for reasons that included adverse events,

loss of complete hematologic response, progression to accelerated or blastic

phase, and loss of MCyR. The dose of imatinib was increased in 75 patients (37%)

during the study period.

>

> Kinase domain (KD) mutations have been associated with an acquired resistance

to tyrosine kinase inhibitors and, during follow-up, 12 different KD mutations

were detected in 11 patients. The development of KD mutations was significant

for predicting loss of CCyR, but not for predicting loss of a complete

hematologic response, progression-free survival, or overall survival. The

researchers also noted that the major predictor for both overall and

progression-free survival was a cytogenetic response at 1 year, which has been

reported previously. " It is difficult to define imatinib failure, in part because

some patients achieve hematologic response rapidly but take substantial time to

achieve a CCyR, " write the authors. " However, it may be inappropriate to wait

indefinitely for a CCyR. "

>

> They point out that in the IRIS study, patients who did not achieve a MCyR but

who discontinued imatinib before loss of a complete hematologic response were

not considered to have failed imatinib therapy. In addition, patients who

stopped treatment because of adverse effects were censored. " Consequently,

event-free survival, as defined in the IRIS study, is likely to be an

overestimate, " they write. " When these failures are considered appropriately, as

in an intention-to-treat analysis, the real response rate to imatinib at 5 years

is 62.7%. "

>

> The study was supported by the Health Research Biomedical Research Centre

Funding Scheme and a grant from the " Fondation de France " The authors have

disclosed no relevant financial relationships.

>

> Entire article can be read at this website:

>

> http://www.medscape.com/viewarticle/577662

<http://www.medscape.com/viewarticle/577662>

>

> Blessings,

>

> Lottie

>

>

[Guest guest]

Hi Everyone.

Just wanted to update you all on my QTc. You may remember that I had the

test abt a week or so ago and it was at 461. a year ago (just before

starting Tasigna) it was 424.

My doctor called yesterday and had me go in for my regular blood tests but

he added magnesium potassium to the list. And he wants me to have another

EKG in a month. He was not alarmed but just wanted to play it safe. My blood

tests all came back last night normal including the mag and potassium. ( I

get my test results within 12 hours on line.Kaiser is wonderful)

I have a question: if my magnesium and potassium were not normal what would

that mean and since they are what does that mean? They said my QTc may

just fluctuate and they will watch me closely. I am so happy to have these

doctors on my side.

Sharon

_____

From: [mailto: ] On Behalf Of Eva

Sent: Saturday, April 25, 2009 9:06 AM

Subject: Re: [ ] Gleevec still the winner

Standing on your head and rubbing your tummy!!! Lottie I'm in. I think we

should take pictures. Whatever works

Luv Eva

From:

Sent: Saturday, April 25, 2009 10:14 AM

groups (DOT) <mailto:%40> com

Subject: Re: [ ] Gleevec still the winner

Dear ,

I think implying Lottie, an 80 year old hellcat, immature is immature. There

wasn't any " politics " in Lottie's naming Gleevec a winner. The stuff didn't

even work for her. She was merely citing Dr. Cortes, a CML expert. I'm quite

sure Lottie wishes she could find a treatment that would beat the beast,

even if that treatment involved standing on her head and rubbing her tummy.

Bob , Granger, Indiana

A 12 Year CML veteran

>

> Patients with CML need all the arsenal at their disposal to have a

fighting chance to beat CML back. Calling one treatment versus another

" winner " is immature at best especially to those who did fail with Gleevec.

Let's keep politics out of CML treatment. The only thing we should all

strive for is that every single CML patient reaches and keeps permanent pcru

with whatever treatment that works! And is that is Gleevec, fine; if it is

another treatment that is equally fine.

> Novartis deserves our accolades for being the first successful treatment.

Period.

>

> [ ] Gleevec still the winner

>

>

>

> Gleevec is still the winner in treating CML. Dr. Cortes wonders what would

be needed to dethrone imatinib as the standard of care for patients with

newly diagnosed CML. He points out that although we would ultimately like to

improve survival, it is unrealistic to expect an improvement in the short

term, given the excellent survival at 5 years for patients treated with

imatinib. " Improving survival free from transformation is similarly

difficult, " he writes. However, an improvement in event-free survival would

be valuable and is a more reachable goal, particularly if a broader

definition of " event free " is used, such as the one suggested by the authors

of the current study, which includes toxicity and failure to achieve (or

loss of) major cytogenetic remission (MCyR) or CCyR.

>

> Most of the available data on imatinib efficacy in newly diagnosed CML

patients is drawn from the International Randomized Study of Interferon

(IRIS), which was conducted under the supervision of the manufacturer. Most

patients achieved a durable CCyR, with an estimated overall survival of 89%

at 5 years, but 20% of patients were censored for various reasons, and

event-free survival and progression to accelerated or blastic phase were

only evaluated for patients who continued to use imatinib.

>

> Comparison with IRIS

>

> Hugues de Lavallade, MD, and colleagues from Hammersmith Hospital and

Imperial College, in London, United Kingdom, performed a single-center trial

that evaluated the efficacy of imatinib in 204 consecutive adult patients

with newly diagnosed BCR-ABL-positive CML in the chronic phase who were

treated from June 2000 until August 2006. The primary goal of their study

was to see whether overall results differed from those obtained from an

analysis performed on an intention-to-treat basis where all events were

recorded. All patients received imatinib as first-line therapy; it was

started within 6 months of their diagnosis. The researchers evaluated

hematologic, cytogenetic, and molecular response, and progression-free and

overall survival.

>

> Even though the median follow-up of 38 months in their study was shorter

than that in the IRIS study, the results were similar. In the IRIS trial,

the cumulative incidence of CCyR at 60 months was 87%, event-free survival

was 83%, and overall survival was 89%. In the current study, the rates were

82.7%, 81.3%, and 83.2%, respectively. After a median of 15.5 months, 54

patients (26%) had permanently discontinued imatinib, for reasons that

included adverse events, loss of complete hematologic response, progression

to accelerated or blastic phase, and loss of MCyR. The dose of imatinib was

increased in 75 patients (37%) during the study period.

>

> Kinase domain (KD) mutations have been associated with an acquired

resistance to tyrosine kinase inhibitors and, during follow-up, 12 different

KD mutations were detected in 11 patients. The development of KD mutations

was significant for predicting loss of CCyR, but not for predicting loss of

a complete hematologic response, progression-free survival, or overall

survival. The researchers also noted that the major predictor for both

overall and progression-free survival was a cytogenetic response at 1 year,

which has been reported previously. " It is difficult to define imatinib

failure, in part because some patients achieve hematologic response rapidly

but take substantial time to achieve a CCyR, " write the authors. " However,

it may be inappropriate to wait indefinitely for a CCyR. "

>

> They point out that in the IRIS study, patients who did not achieve a MCyR

but who discontinued imatinib before loss of a complete hematologic response

were not considered to have failed imatinib therapy. In addition, patients

who stopped treatment because of adverse effects were censored.

" Consequently, event-free survival, as defined in the IRIS study, is likely

to be an overestimate, " they write. " When these failures are considered

appropriately, as in an intention-to-treat analysis, the real response rate

to imatinib at 5 years is 62.7%. "

>

> The study was supported by the Health Research Biomedical Research Centre

Funding Scheme and a grant from the " Fondation de France " The authors have

disclosed no relevant financial relationships.

>

> Entire article can be read at this website:

>

> http://www.medscape <http://www.medscape.com/viewarticle/577662>

..com/viewarticle/577662 <http://www.medscape

<http://www.medscape.com/viewarticle/577662> .com/viewarticle/577662>

>

> Blessings,

>

> Lottie

>

>

[Guest guest]

I am very happy for you . Way to go Sharon!! You are lucky to have such great

doctors.

Eva

From: Sharon Teichera

Sent: Saturday, April 25, 2009 12:15 PM

Subject: RE: [ ] Gleevec still the winner

Hi Everyone.

Just wanted to update you all on my QTc. You may remember that I had the

test abt a week or so ago and it was at 461. a year ago (just before

starting Tasigna) it was 424.

My doctor called yesterday and had me go in for my regular blood tests but

he added magnesium potassium to the list. And he wants me to have another

EKG in a month. He was not alarmed but just wanted to play it safe. My blood

tests all came back last night normal including the mag and potassium. ( I

get my test results within 12 hours on line.Kaiser is wonderful)

I have a question: if my magnesium and potassium were not normal what would

that mean and since they are what does that mean? They said my QTc may

just fluctuate and they will watch me closely. I am so happy to have these

doctors on my side.

Sharon

_____

From: [mailto: ] On Behalf Of Eva

Sent: Saturday, April 25, 2009 9:06 AM

Subject: Re: [ ] Gleevec still the winner

Standing on your head and rubbing your tummy!!! Lottie I'm in. I think we

should take pictures. Whatever works

Luv Eva

From:

Sent: Saturday, April 25, 2009 10:14 AM

groups (DOT) <mailto:%40> com

Subject: Re: [ ] Gleevec still the winner

Dear ,

I think implying Lottie, an 80 year old hellcat, immature is immature. There

wasn't any " politics " in Lottie's naming Gleevec a winner. The stuff didn't

even work for her. She was merely citing Dr. Cortes, a CML expert. I'm quite

sure Lottie wishes she could find a treatment that would beat the beast,

even if that treatment involved standing on her head and rubbing her tummy.

Bob , Granger, Indiana

A 12 Year CML veteran

>

> Patients with CML need all the arsenal at their disposal to have a

fighting chance to beat CML back. Calling one treatment versus another

" winner " is immature at best especially to those who did fail with Gleevec.

Let's keep politics out of CML treatment. The only thing we should all

strive for is that every single CML patient reaches and keeps permanent pcru

with whatever treatment that works! And is that is Gleevec, fine; if it is

another treatment that is equally fine.

> Novartis deserves our accolades for being the first successful treatment.

Period.

>

> [ ] Gleevec still the winner

>

>

>

> Gleevec is still the winner in treating CML. Dr. Cortes wonders what would

be needed to dethrone imatinib as the standard of care for patients with

newly diagnosed CML. He points out that although we would ultimately like to

improve survival, it is unrealistic to expect an improvement in the short

term, given the excellent survival at 5 years for patients treated with

imatinib. " Improving survival free from transformation is similarly

difficult, " he writes. However, an improvement in event-free survival would

be valuable and is a more reachable goal, particularly if a broader

definition of " event free " is used, such as the one suggested by the authors

of the current study, which includes toxicity and failure to achieve (or

loss of) major cytogenetic remission (MCyR) or CCyR.

>

> Most of the available data on imatinib efficacy in newly diagnosed CML

patients is drawn from the International Randomized Study of Interferon

(IRIS), which was conducted under the supervision of the manufacturer. Most

patients achieved a durable CCyR, with an estimated overall survival of 89%

at 5 years, but 20% of patients were censored for various reasons, and

event-free survival and progression to accelerated or blastic phase were

only evaluated for patients who continued to use imatinib.

>

> Comparison with IRIS

>

> Hugues de Lavallade, MD, and colleagues from Hammersmith Hospital and

Imperial College, in London, United Kingdom, performed a single-center trial

that evaluated the efficacy of imatinib in 204 consecutive adult patients

with newly diagnosed BCR-ABL-positive CML in the chronic phase who were

treated from June 2000 until August 2006. The primary goal of their study

was to see whether overall results differed from those obtained from an

analysis performed on an intention-to-treat basis where all events were

recorded. All patients received imatinib as first-line therapy; it was

started within 6 months of their diagnosis. The researchers evaluated

hematologic, cytogenetic, and molecular response, and progression-free and

overall survival.

>

> Even though the median follow-up of 38 months in their study was shorter

than that in the IRIS study, the results were similar. In the IRIS trial,

the cumulative incidence of CCyR at 60 months was 87%, event-free survival

was 83%, and overall survival was 89%. In the current study, the rates were

82.7%, 81.3%, and 83.2%, respectively. After a median of 15.5 months, 54

patients (26%) had permanently discontinued imatinib, for reasons that

included adverse events, loss of complete hematologic response, progression

to accelerated or blastic phase, and loss of MCyR. The dose of imatinib was

increased in 75 patients (37%) during the study period.

>

> Kinase domain (KD) mutations have been associated with an acquired

resistance to tyrosine kinase inhibitors and, during follow-up, 12 different

KD mutations were detected in 11 patients. The development of KD mutations

was significant for predicting loss of CCyR, but not for predicting loss of

a complete hematologic response, progression-free survival, or overall

survival. The researchers also noted that the major predictor for both

overall and progression-free survival was a cytogenetic response at 1 year,

which has been reported previously. " It is difficult to define imatinib

failure, in part because some patients achieve hematologic response rapidly

but take substantial time to achieve a CCyR, " write the authors. " However,

it may be inappropriate to wait indefinitely for a CCyR. "

>

> They point out that in the IRIS study, patients who did not achieve a MCyR

but who discontinued imatinib before loss of a complete hematologic response

were not considered to have failed imatinib therapy. In addition, patients

who stopped treatment because of adverse effects were censored.

" Consequently, event-free survival, as defined in the IRIS study, is likely

to be an overestimate, " they write. " When these failures are considered

appropriately, as in an intention-to-treat analysis, the real response rate

to imatinib at 5 years is 62.7%. "

>

> The study was supported by the Health Research Biomedical Research Centre

Funding Scheme and a grant from the " Fondation de France " The authors have

disclosed no relevant financial relationships.

>

> Entire article can be read at this website:

>

> http://www.medscape <http://www.medscape.com/viewarticle/577662>

..com/viewarticle/577662 <http://www.medscape

<http://www.medscape.com/viewarticle/577662> .com/viewarticle/577662>

>

> Blessings,

>

> Lottie

>

>

[Guest guest]

Yes...

As far as the standing on her head a rubbing her tummy... I am sure back in the

day Lottie could do it. Maybe after her next pain shot she will try it!

I have never been on gleevec but there is no denying that it changed the course

of treatment for CML and likely other cancers. It is a winner in a collection

of winners! In my humble opinion anyway...

Rhonda

Sent from my Verizon Wireless BlackBerry

[ ] Gleevec still the winner

>

>

>

> Gleevec is still the winner in treating CML. Dr. Cortes wonders what would be

needed to dethrone imatinib as the standard of care for patients with newly

diagnosed CML. He points out that although we would ultimately like to improve

survival, it is unrealistic to expect an improvement in the short term, given

the excellent survival at 5 years for patients treated with imatinib. " Improving

survival free from transformation is similarly difficult, " he writes. However,

an improvement in event-free survival would be valuable and is a more reachable

goal, particularly if a broader definition of " event free " is used, such as the

one suggested by the authors of the current study, which includes toxicity and

failure to achieve (or loss of) major cytogenetic remission (MCyR) or CCyR.

>

> Most of the available data on imatinib efficacy in newly diagnosed CML

patients is drawn from the International Randomized Study of Interferon (IRIS),

which was conducted under the supervision of the manufacturer. Most patients

achieved a durable CCyR, with an estimated overall survival of 89% at 5 years,

but 20% of patients were censored for various reasons, and event-free survival

and progression to accelerated or blastic phase were only evaluated for patients

who continued to use imatinib.

>

> Comparison with IRIS

>

> Hugues de Lavallade, MD, and colleagues from Hammersmith Hospital and Imperial

College, in London, United Kingdom, performed a single-center trial that

evaluated the efficacy of imatinib in 204 consecutive adult patients with newly

diagnosed BCR-ABL-positive CML in the chronic phase who were treated from June

2000 until August 2006. The primary goal of their study was to see whether

overall results differed from those obtained from an analysis performed on an

intention-to-treat basis where all events were recorded. All patients received

imatinib as first-line therapy; it was started within 6 months of their

diagnosis. The researchers evaluated hematologic, cytogenetic, and molecular

response, and progression-free and overall survival.

>

> Even though the median follow-up of 38 months in their study was shorter than

that in the IRIS study, the results were similar. In the IRIS trial, the

cumulative incidence of CCyR at 60 months was 87%, event-free survival was 83%,

and overall survival was 89%. In the current study, the rates were 82.7%, 81.3%,

and 83.2%, respectively. After a median of 15.5 months, 54 patients (26%) had

permanently discontinued imatinib, for reasons that included adverse events,

loss of complete hematologic response, progression to accelerated or blastic

phase, and loss of MCyR. The dose of imatinib was increased in 75 patients (37%)

during the study period.

>

> Kinase domain (KD) mutations have been associated with an acquired resistance

to tyrosine kinase inhibitors and, during follow-up, 12 different KD mutations

were detected in 11 patients. The development of KD mutations was significant

for predicting loss of CCyR, but not for predicting loss of a complete

hematologic response, progression-free survival, or overall survival. The

researchers also noted that the major predictor for both overall and

progression-free survival was a cytogenetic response at 1 year, which has been

reported previously. " It is difficult to define imatinib failure, in part because

some patients achieve hematologic response rapidly but take substantial time to

achieve a CCyR, " write the authors. " However, it may be inappropriate to wait

indefinitely for a CCyR. "

>

> They point out that in the IRIS study, patients who did not achieve a MCyR but

who discontinued imatinib before loss of a complete hematologic response were

not considered to have failed imatinib therapy. In addition, patients who

stopped treatment because of adverse effects were censored. " Consequently,

event-free survival, as defined in the IRIS study, is likely to be an

overestimate, " they write. " When these failures are considered appropriately, as

in an intention-to-treat analysis, the real response rate to imatinib at 5 years

is 62.7%. "

>

> The study was supported by the Health Research Biomedical Research Centre

Funding Scheme and a grant from the " Fondation de France " The authors have

disclosed no relevant financial relationships.

>

> Entire article can be read at this website:

>

> http://www.medscape.com/viewarticle/577662

<http://www.medscape.com/viewarticle/577662>

>

> Blessings,

>

> Lottie

>

>

[Guest guest]

Hi ,

I wouldn't call it a winner, I would call it a BLOCKBUSTER!!!

If it wasn't for Dr. Druker and his persistance we wouldn't have Gleevec. If

we didn't have Gleevec, there would be no Sprycel, Tasigna, etc.

Also, I don't know if achieving PCRU is a goal that we should be striving

for. Less than 10% actually achieve it. A 3 log reduction is just as good

when it comes to survival. In fact, maintaing CCR over a long period of time

produces the same longevity results as reaching PCRU.

Zavie

Zavie (age 70)

67 Shoreham Avenue

Ottawa, Canada, K2G 3X3

dxd AUG/99

INF OCT/99 to FEB/00, CHF

No meds FEB/00 to JAN/01

Gleevec since MAR/27/01 (400 mg)

CCR SEP/01. #102 in Zero Club

2.8 log reduction Sep/05

3.0 log reduction Jan/06

2.9 log reduction Feb/07

3.6 log reduction Apr/08

3.6 log reduction Sep/08

e-mail: zmiller@...

Tel: 613-726-1117

Tel: 561-429-3309 in Florida

Fax: 309-296-0807

Cell: 613-282-0204

ID: zaviem

YM: zaviemiller

Skype: Zavie

_____

From: [mailto: ] On Behalf Of

Rutigliano,

Sent: April-24-09 9:22 AM

Subject: RE: [ ] Gleevec still the winner

Patients with CML need all the arsenal at their disposal to have a fighting

chance to beat CML back. Calling one treatment versus another " winner " is

immature at best especially to those who did fail with Gleevec. Let's keep

politics out of CML treatment. The only thing we should all strive for is

that every single CML patient reaches and keeps permanent pcru with whatever

treatment that works! And is that is Gleevec, fine; if it is another

treatment that is equally fine.

Novartis deserves our accolades for being the first successful treatment.

Period.

[ ] Gleevec still the winner

Gleevec is still the winner in treating CML. Dr. Cortes wonders what would

be needed to dethrone imatinib as the standard of care for patients with

newly diagnosed CML. He points out that although we would ultimately like to

improve survival, it is unrealistic to expect an improvement in the short

term, given the excellent survival at 5 years for patients treated with

imatinib. " Improving survival free from transformation is similarly

difficult, " he writes. However, an improvement in event-free survival would

be valuable and is a more reachable goal, particularly if a broader

definition of " event free " is used, such as the one suggested by the authors

of the current study, which includes toxicity and failure to achieve (or

loss of) major cytogenetic remission (MCyR) or CCyR.

Most of the available data on imatinib efficacy in newly diagnosed CML

patients is drawn from the International Randomized Study of Interferon

(IRIS), which was conducted under the supervision of the manufacturer. Most

patients achieved a durable CCyR, with an estimated overall survival of 89%

at 5 years, but 20% of patients were censored for various reasons, and

event-free survival and progression to accelerated or blastic phase were

only evaluated for patients who continued to use imatinib.

Comparison with IRIS

Hugues de Lavallade, MD, and colleagues from Hammersmith Hospital and

Imperial College, in London, United Kingdom, performed a single-center trial

that evaluated the efficacy of imatinib in 204 consecutive adult patients

with newly diagnosed BCR-ABL-positive CML in the chronic phase who were

treated from June 2000 until August 2006. The primary goal of their study

was to see whether overall results differed from those obtained from an

analysis performed on an intention-to-treat basis where all events were

recorded. All patients received imatinib as first-line therapy; it was

started within 6 months of their diagnosis. The researchers evaluated

hematologic, cytogenetic, and molecular response, and progression-free and

overall survival.

Even though the median follow-up of 38 months in their study was shorter

than that in the IRIS study, the results were similar. In the IRIS trial,

the cumulative incidence of CCyR at 60 months was 87%, event-free survival

was 83%, and overall survival was 89%. In the current study, the rates were

82.7%, 81.3%, and 83.2%, respectively. After a median of 15.5 months, 54

patients (26%) had permanently discontinued imatinib, for reasons that

included adverse events, loss of complete hematologic response, progression

to accelerated or blastic phase, and loss of MCyR. The dose of imatinib was

increased in 75 patients (37%) during the study period.

Kinase domain (KD) mutations have been associated with an acquired

resistance to tyrosine kinase inhibitors and, during follow-up, 12 different

KD mutations were detected in 11 patients. The development of KD mutations

was significant for predicting loss of CCyR, but not for predicting loss of

a complete hematologic response, progression-free survival, or overall

survival. The researchers also noted that the major predictor for both

overall and progression-free survival was a cytogenetic response at 1 year,

which has been reported previously. " It is difficult to define imatinib

failure, in part because some patients achieve hematologic response rapidly

but take substantial time to achieve a CCyR, " write the authors. " However,

it may be inappropriate to wait indefinitely for a CCyR. "

They point out that in the IRIS study, patients who did not achieve a MCyR

but who discontinued imatinib before loss of a complete hematologic response

were not considered to have failed imatinib therapy. In addition, patients

who stopped treatment because of adverse effects were censored.

" Consequently, event-free survival, as defined in the IRIS study, is likely

to be an overestimate, " they write. " When these failures are considered

appropriately, as in an intention-to-treat analysis, the real response rate

to imatinib at 5 years is 62.7%. "

The study was supported by the Health Research Biomedical Research Centre

Funding Scheme and a grant from the " Fondation de France " The authors have

disclosed no relevant financial relationships.

Entire article can be read at this website:

http://www.medscape <http://www.medscape.com/viewarticle/577662>

..com/viewarticle/577662 <http://www.medscape

<http://www.medscape.com/viewarticle/577662> .com/viewarticle/577662>

Blessings,

Lottie