Triple Therapy: New Standard for CLL?

[Guest guest]

Triple Therapy: New Standard for CLL?

n = 817 adults seen at more than 100 centers in 11 countries who were

followed for a median of 26 months. Their mean age was 61 years, with a

range of 36 to 81 years.

http://tinyurl.com/5wh8xh

[Guest guest]

Please be so kind to send me the link to

this article. The one you posted did not work. I am very interested to read it.

Thanks.

Aviva

From:

[mailto: ] On Behalf Of karlamonyc

Sent: Thursday, December 11, 2008

3:45 PM

Subject: Triple Therapy:

New Standard for CLL?

Triple Therapy: New Standard for CLL?

n = 817 adults seen at more than 100 centers in 11 countries who were

followed for a median of 26 months. Their mean age was 61 years, with a

range of 36 to 81 years.

http://tinyurl.com/5wh8xh

[Guest guest]

Sorry, try this one: http://tinyurl.com/6eaph7

It may require a free registration. If so I'll copy it here.

~ Karl

[Guest guest]

The link didn't work for me either!

Thanks

carol

RE: Triple Therapy: New Standard for CLL?

Please be so kind to send me the link to this article. The one you posted did not work. I am very interested to read it.

Thanks.

Aviva

From: [mailto: ] On Behalf Of karlamonycSent: Thursday, December 11, 2008 3:45 PM Subject: Triple Therapy: New Standard for CLL?

Triple Therapy: New Standard for CLL?n = 817 adults seen at more than 100 centers in 11 countries who were followed for a median of 26 months. Their mean age was 61 years, with a range of 36 to 81 years.http://tinyurl.com/5wh8xh

[Guest guest]

Savy request, Helene ... the source being generally less prone to

bias. Seek also peer correspondence.

We have a link to the ASH abstract, which contains more detail - but

does not measure up to a report published in a major journal. PS. I

think of all the reviews, none compare in rigor to FDA review for

marketing approval.

See http://www.lymphomation.org/current.htm

~ Karl

>

> Is there somewhere this whole study is reported, rather than just

the

> summary? I would like to know how many unmutated persons responded

and

> for how long, for example? And other features as well.

> Also, is this ongoing to look for survival differences?

> And is there another study out there comparting FR to FCR? which

seems

> a more commmon head-to-head comparison.

>

> Also, why the study results are certainly news from a large

randomized

> trial, I don't understand the comments about this study changing

> practice. Almost everyone gets FCR now and has been for years.

>

> What I am missing?

>

> Helene

>

[Guest guest]

Thanks Karl,

I'd be happy with easier access to full studies, patient

characteristics, years followed, full methods, etc...even if they

aren't good enough for FDA. If I can read all the facts, I can make up

my own mind on how convincing/hopeful/or just hype it is.

Helene

[Guest guest]

Hi, The same study could be sufficient for FDA approval, can't

say. .. I was referring to how comprehensive the FDA review process

is, relative to the review at a clinical Journal, or for acceptance

at ASH. ASH would have the lower bar, in part because they are

reviewing many hundreds of abstracts! in a short time.

Karl

>

> Thanks Karl,

>

> I'd be happy with easier access to full studies, patient

> characteristics, years followed, full methods, etc...even if they

> aren't good enough for FDA. If I can read all the facts, I can

make

up

> my own mind on how convincing/hopeful/or just hype it is.

>

> Helene

>

[Guest guest]

This study, comparing FC versus FCR represents important " issues "

with the systems in place governing:

1. determination of the " standard of care "

2. FDA approval

3. inurance willingness to cover a treatment

FC versus FCR has no impact on the care provided in the United

States. It will possible lead to a dramatic increase in the use of

rituximab in Europe, where most patients do not automatically receive

rituximab.

It may also provide data that will be used to obtain FDA approval for

FCR, obligating insurers to pay for the rituximab. But this last one

is not much of an issue as most insurers will cover the rituximab.

Not everyone in the US uses FCR as many still use FR. While FCR

demonstrates improved response rates compared to FR, no has

demonstrated improved survival, which is the more important measure.

It is important to remember the more toxic therapy might yield better

responses, but leave patients unable to tolerate much else afterwards.

My personal belief is to make CLL as chronic of a disease as

possible. More important than obtaining a response is keeping the

patient symptom free and able to live life with the highest quality

of life as possible.

There are several studies looking at FCR versus FR, the largest is a

cooperative group trial, but these results will not be available for

a very long time. Overall, the information from ASH was fairly

uninteresting. The other large study presented compared PCR to FCR.

This study used lower doses of fludarabine than almost what everyone

else uses. The study demonstrated no difference in toxicities or

outcomes. But its applicability is certainly limited.

Rick Furman, MD

> >

> > Thanks Karl,

> >

> > I'd be happy with easier access to full studies, patient

> > characteristics, years followed, full methods, etc...even if they

> > aren't good enough for FDA. If I can read all the facts, I can

> make

> up

> > my own mind on how convincing/hopeful/or just hype it is.

> >

> > Helene

> >

>

[Guest guest]

Appreciate your comments, Ellen. Similarly, I think, it's been

observed that people who are less optimistic do poorly when fighting

disease. So some will conclude that being pessimistic causes poor

outcomes. It might contribute, but this observation doesn't prove

that because people who are not feeling well may be more seriously

ill, and will be less inclinded to optimism. That is, pessimism

could be a marker for having more advanced disease ... as could

initial use of FCR .. as you point out.

Karl

>

> Memorial Sloan-Kettering has been using FCR as a first-line

treatment

> for years; 8 yrs ago when I first needed tx it was the only

treatment

> MSK offered me in 2000. I switched hospitals and did a different

> therapy. Just observation over the past 10 yrs as a member of a

CLL

> chatlist—many of whose members chose FCR as their first tx—led me

to

> believe that a) FCR had the best and longest CR rate of any other

known

> tx for CLL and a sizeable # of people treated with FCR had

trouble

> finding effective treatments when out of remission and often

appeared

> to develop serious treatment-related complications over the next

couple

> of years that often led to death. I wasn't particularly surprised

to

> find that FCR hadn't been shown to lengthen our life expectancy.

>

> But I also observed that often (though not always) the people who

opted

> for FCR rather than milder treatments were those whose disease

symptoms

> were worrisome enough to require the solid, fast punch of two

strong

> chemo agents (FC) and a biological agent ® that boostd the

efficacy

> of that combination of chemos. For that reason, stats regarding

the

> prognostic indicators Dan mentions in his intro, as they relate to

the

> 2-yr follow up results (though I think the mean # yrs for duration

of

> CR for FCR may be 3) would be important—for showing if there's any

> relationship between the predicted course of the disease before FCR

> therapy and duration of CR and subsequent response to future tx

after

> FCR.

> -ellen d.

>

> > Thanks Karl,

> >

> > I'd be happy with easier access to full studies, patient

> > characteristics, years followed, full methods, etc...even if they

> > aren't good enough for FDA. If I can read all the facts, I can

make up

> > my own mind on how convincing/hopeful/or just hype it is.

> >

> > Helene

> >

> >

> >

>

[Guest guest]

Dr. Furman brings up a really important point - the choice between

hitting hard for the best response (which may be your first and best

shot), and treating CLL as chronic, so tamping it down to QOL and

general health stays as good as possible.

Where I feeling very sick, I'd go for FCR. For those of us who feel

good, but have numbers moving badly, it seems much more appealing to do

something milder.

I am very interested in people discussing their choices to do one of

the other.

Helene

[Guest guest]

Dear Helene,

I chose just fludarabine. I'm not sure why I didn't select fludara +

rituxan, I don't recall whether it was discussed with me or not. I

knew that chances for a CR were slim to none with fludara alone but my

fears about treatment plus my lack of sickness—I just wasn't feeling

that bad! (but my swollen nodes were awfully big)—made me want to sneak

into the whole thing. I'm not sure what else I was thinking -- it was

8 yrs ago.

I also elected to stop the treatment almost as soon as the nodes went

down, after only 3 of 6 rounds. My hem/onc at the time, while not

completely happy with it, both respected my certainty about what I

wanted and also acknowledged that with fludara alone there really was

no evidence one way or the other that more rounds would bring better

results. The whole truth was that a partial remission in my case

meant the disease started " back " almost immediately. But in the

meanwhile, I enjoyed a good year of normal counts and nodes that grew

back slowly enough to allow me to lead a normal life.

The second time I had tx, I did fludara + rituxan. It might have

worked longer/better as a first line treatment. As it was, and again I

stopped early after 4 rounds, I got about 9 months of pretty normal

life. Rituxan alone twice bought me several more months. At that

point, my doctor thought that rather than do FCR or something stronger,

probably the only realistic alternatives, I was a good candidate for

Dr. Furman's trial for thalidomide and fludarabine. Thalidomide had

proven successful, in combination with other different drugs, in giving

several patients with multiple myeloma some good remissions.

Luckily I was assigned to the arm that did both fludarabine and

thalidomide, not just thalidomide. It's now been 4 yrs since I stopped

the fludarabine and over 3 yrs since I stopped taking

thalidomide. I've been in a complete remission the whole time. That

time, I did all 6 rounds! Hope this is of some interest. It should

be, remembering that revlamid is now the drug most like thalidomide,

with fewer detrimental side effects.

-Ellen D.

On Dec 12, 2008, at 8:53 PM, elmerleb wrote:

> Ellen,

> I found your post so helpful. I am also looking for how to connect

> prognostic or cytogenic features to what can be expected duration of

> response to FCR.

>

> At the recent Lymphoma conference (I remember you there), both Drs.

> Furman and Rai expressed preference for FR over FCR except in some

> instances.

>

> If you don't mind saying, what did you choose instead of FCR?

>

> I also learned that Sloan is (or was) pushing FCR. I had thought

> they were PCR folks.

>

> In reference to what Karl mentioned, I think it is fine for ASH to

> have less rigorous standards. I think hearing things that are early,

> or not fully tested, can be tremendously interesting. As long as we

> know what methods were used, we don't need every study to be

> randomized prospective controls. There is much to be learned from

> things not rigorous enough approvals, but " heuristics " that show us

> where things could go.

>

> Now, I understand some centers of Bendamustine & R as firstline. So,

> when would one choose which? Studies to date don't make these kinds

> of comparisons. They will get there, but I'd like more now!

>

> Sorry to go on....the research is my main focus.

>

> Helene

>

>

>