Re: More from ASH - Deininger's talk

[Guest guest]

Once again, thank you so much for taking the time to share all of this

with us. I have a few comments on this latest report:

Rockefeller <rrockef1@...> wrote: • We don’t yet know

whether we can stop clock of CML progression with IM, or just delay it (note

from me: the pendulum of belief is clearly swinging toward believing that we can

stop it.

What an exciting thought! I hope it pans out to be that we can actually

halt the progression. Wow, the thought of it just makes me want to jump

• We’re getting better at predicting relapse. One way is by following the

phosphorylation of CRKL (pronounced “crackleâ€) – one of the enzymes that

bcr-abl works on downstream by putting a phosphate group onto it. When

phospo-CRKLstarts going up, you know that bcr-abl is no longer being inhibited.

I’m not sure what clinical utility this has (I don’t know of any docs

measuring phospho-CRKL on their patients), but it was interesting…

This sounds like it could be of such important clinical value (if they

actually measured the phosphorylation). Any idea why they aren't doing it?

Unfortunately, one relatively common mutation, called T315I (how annoying

these names can be!), is a real baddie: it not only confers resistance to IM,

desatinib and AMN107, but it heralds advancing disease.

Was there any news on the new drug that was rumoured to be in trials (or soon

to be in trials) that specifically targets this mutation?

• Novartis believes that a critical factor in IM resistance is poor adherence

by patients. According to them, some 30% of the medication prescribed is not

actually taken.

Do you mean that people aren't consistant with taking their Gleevec (some days

they take it, others they don't) or that they'll take half as much as they're

supposed to? Or perhaps both? We can't always blame the patients either

(unfortunately), it seems that there are still some doctors out there who aren't

familliar enough with Gleevec and are still playing around with sub theraputic

doses or playing the intermittent game (take it when you feel like it or don't

take it if you don't feel like it etc).

Also, how did they come to this conclusion? Is it from interviewing patients

or by comparing written prescriptions with orders put in by the pharmacies?

Sounds kinda high to me, so I wonder what criteria they used to form this

conclusion. Is someone who missed one dose in 6 months considered to be

non-complient or does it take a couple of doses? I just wonder how they define

" poor adherence " .

With much appreciation for your time and insight,

Tracey

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