Re: Dr. Goldman's talk on May 24th in Montreal

[Guest guest]

Cheryl-Anne and Suzan,

Dr. Goldman is very accessible and I think would answer your outstanding

questions by email. If you'll write to me privately I'll give it to you although

you probably already have it. Or, if you have questions you'd like to have

covered I'd be happy to follow up at my next appointment with him which is June

30. In addition to blood work, interview with an intern, I always have a good

long time to chat with Dr. Goldman.

L

[ ] Dr. Goldman's talk on May 24th in Montreal

Dr Goldman's talk - May 24, 2006 - Montreal

As mentioned in my previous message, essentially Dr. Goldman covered a short

history of CML and then talked about current approaches to treatment. When

it came to the question of how Gleevec made it to expanded clinical trials,

he thought it was his patient in the UK who started a petition on line. We

pointed out that it was our very own Suzan McNamara who was present with us.

He was thankful that we corrected him. Afterwards we were thinking that

perhaps he was thinking about the petition in the UK?

He fielded a number of questions:

We brought up our interest in immunotherapy, and knowing that he is

currently working in this area we were quite interested to hear what he

might have to say. He told us that he is just in the very preliminary

stages of getting a clinical trial underway. He was quite cautious to give

us too many details, so we will just have to keep a watch out for more news

in the future. As you can imagine, this area of research is quite

competitive!

Interestingly, he stated, rather convincingly too, that he felt that perhaps

we might find in the future that some patients, albeit a very small

fraction, might be able to stop IM (but only after several years of

continuous PCRU - is there anyone who has achieved several years of

continuous PCRU, without any fluctuations?)and maintain undetectable level

remission similar to INF. He is interested to find out, as others are, why

this may be so. He emphasized however, that patients should not stop IM

because most patients relapse fairly quickly. We will have to keep our eyes

open for any new data about this.

He was asked about pregnancy (we have a few young patients in our group).

He told us that there have been a number of cases of mothers with CML on IM

who have become pregnant and that this data is being tracked quite closely

at Novartis. He pointed out that some of the pregnancies have resulted in

normal healthy births and children. He spoke about one case where the

patient was already 9 weeks pregnant and was on IM. Of course the first

trimester is where IM would pose the most teratogenic risk, so it is more

like a case of shutting the barn door after the horse is already out.

However, after careful consideration and consultation with Novartis (who

advised/suggested a therapeutic abortion) the decision was to stop IM and

allow the pregnancy to continue. Mother and baby are fine and the mother

re-started IM 4 months after the baby was delivered. He also mentioned that

there were reports of spontaneous abortions, and foetal malformations, so

while there have been a number of live healthy births, the recommendation is

to avoid Gleevec and pregnancy, er, I mean avoid getting pregnant while on

Gleevec ;>)! Otherwise, I personally have no problem avoiding Gleevec and

Pregnancy!!!! <just too funny, I couldn't resist>

We asked what is the significance, if any, of having hypocellular marrow for

years while undergoing Gleevec therapy? Do you think that there will be any

long term adverse effects from this? Dr. Goldman that it is something that

is common, but that there doesn't seem to be anything to worry about.

There was a question about at what point can a patient safely reduce the

dose of IM? These would be patients who started on a 600 mg or 800 mg dose

and achieved CCR. These are patients whose QOL is compromised because of

side effects from IM. His response was that the dose should not be reduced

as there is no data that would support doing so.

We asked about our concern with staying on IM (or any other drug for that

matter) for significant durations of time at very low or undetectable levels

of disease. The concern of course being that even at PCRU there are still

quite a few CML cells that could potentially wreak havoc at some time in the

future. He seemed to be less concerned with this, saying that as long as

you have a 3 log or better reduction you should just stay with IM. In

thinking about this, I wish we could have been more clear with him. We

really wanted him to talk about a true cure.

On the subject of hormone issues with Gleevec therapy. e.g. missed menstrual

cycles, heavy periods, breast enlargement, he really didn't have much to add

about this but if I remember correctly, he did say that Novartis was

tracking this.

He basically said that Dasatinib and Nilotinib are essentially the same

drugs with regards to performance, although I do not quite understand how

that could be so. I think it is a bit premature to say that as Dasatinib

has been used on more patients than Nilotinib. However, we just have to

remember that this was his opinion and he reminded us that his opinion might

vary from ours and our treating doctors opinion.

We thanked Novartis for sponsoring Dr. Goldman, in fact someone from

Novartis joined us, which was a bit of a surprise, it did change the tone of

the meeting though. We've had some of our best productive meetings when it

is just us patients with our doctors.

Dr. Goldman is a delightful person and we were very happy to meet him. We

thanked him and gave both he and Dr. Pierre Laneuville each a very nice

bottle of wine with cards signed by all of us. We hope Dr. Goldman will

come back and visit us again as a guest of the CML Society.

I should mention that the CML Society is holding our first board meeting

next week and we will be putting together our agenda of activities for this

coming year. We will be posting the minutes and updating the website so,

stay tuned.

Cheryl-Anne and Suzan

[Guest guest]

At 07:56 AM 5/28/06 -0400, you wrote:

>He basically said that Dasatinib and Nilotinib are essentially the same

>drugs with regards to performance, although I do not quite understand how

>that could be so. I think it is a bit premature to say that as Dasatinib

>has been used on more patients than Nilotinib. However, we just have to

>remember that this was his opinion and he reminded us that his opinion might

>vary from ours and our treating doctors opinion.

Hi Cheryl-Anne,

Thanks for your report.

About the above comment.....Dr. Druker has expressed the same. He thinks that

both BMS and AMN will be comparable and his reasoning as explained to me:

BMS (I am not used to calling it dasatinib or Sprycel yet) is supposed to

be maybe 100x more potent than IM (?in the lab) and AMN is supposed to be ?

10x more potent.....but Dr. Druker says the difference will be in the dose.

If you only take 100-140mg of BMS but you take 1200mg of AMN, it evens out.

Also, he does not think that the 2nd pathway of BMS is playing that

significant of a role....the better efficacy of these drugs is that they

bind better. Also, he wondered if the 2nd pathway (the SCR) was causing the

problem with the low platelets because it did not seem that they were

having the same problem with AMN.

So, he does agree with Dr. Goldman and thinks that these 2 new drugs will

be comparable.

Thanks again for your report,

Maui Nanc

[Guest guest]

Hi ,

Thanks for your comments, yes he is very approachable and I will

probably bump into him at ASCO this weekend.

If I still have some quesitons, I will be sure to e-mail you so you

can go through them with him on your visit.

Cheers and all the best to you,

Cheryl-Anne

>

> Cheryl-Anne and Suzan,

>

> Dr. Goldman is very accessible and I think would answer your

outstanding questions by email. If you'll write to me privately I'll

give it to you although you probably already have it. Or, if you

have questions you'd like to have covered I'd be happy to follow up

at my next appointment with him which is June 30. In addition to

blood work, interview with an intern, I always have a good long time

to chat with Dr. Goldman.

>

> L

> ----- Original Message -----

[Guest guest]

Hi ,

Thanks for providing us with Dr. Druker's perspective, it does help

clear things up. I guess the other thing that is puzzling is that I

do know of some patients who were on the AMN trial and really had no

success at all and are doing very well on Dastanib. So, I am not

sure if in some cases, particularly in patients who have had the

disease for quite some time if the SRC pathway is beneficial for

them. As for the platelets, I know of some patients on AMN who are

having trouble with that as well.

In time it will be interesting to see what will actually prevail.

It's nice to have choices for those who need them.

Peace and Love,

Cheryl-Anne

> >He basically said that Dasatinib and Nilotinib are essentially the

same

> >drugs with regards to performance, although I do not quite

understand how

> >that could be so. I think it is a bit premature to say that as

Dasatinib

> >has been used on more patients than Nilotinib. However, we just

have to

> >remember that this was his opinion and he reminded us that his

opinion might

> >vary from ours and our treating doctors opinion.

>

>

> Hi Cheryl-Anne,

>

> Thanks for your report.

> About the above comment.....Dr. Druker has expressed the same. He

thinks that

> both BMS and AMN will be comparable and his reasoning as explained

to me:

>

> BMS (I am not used to calling it dasatinib or Sprycel yet) is

supposed to

> be maybe 100x more potent than IM (?in the lab) and AMN is supposed

to be ?

> 10x more potent.....but Dr. Druker says the difference will be in

the dose.

> If you only take 100-140mg of BMS but you take 1200mg of AMN, it

evens out.

> Also, he does not think that the 2nd pathway of BMS is playing that

> significant of a role....the better efficacy of these drugs is that

they

> bind better. Also, he wondered if the 2nd pathway (the SCR) was

causing the

> problem with the low platelets because it did not seem that they

were

> having the same problem with AMN.

> So, he does agree with Dr. Goldman and thinks that these 2 new

drugs will

> be comparable.

>

> Thanks again for your report,

> Maui Nanc

>

[Guest guest]

At 02:04 AM 5/30/06 +0000, you wrote:

>Thanks for providing us with Dr. Druker's perspective, it does help

>clear things up. I guess the other thing that is puzzling is that I

>do know of some patients who were on the AMN trial and really had no

>success at all and are doing very well on Dastanib. So, I am not

>sure if in some cases, particularly in patients who have had the

>disease for quite some time if the SRC pathway is beneficial for

>them. As for the platelets, I know of some patients on AMN who are

>having trouble with that as well.

Hi Cheryl-Anne,

If I am remembering correctly, those were things he told me about 6 months

ago when I was trying to decide whether to do the BMS trial or the AMN

trial....and we know how things change in the CML world in 6 months! but he

does seem to downplay the SRC pathway. Last visit, he told me he would have

more BMS stats from the ?ASCO conference....like whether they were seeing

better results with the single larger dose or the split even dose. It takes

a lot of patients to see a trend and not just an individual

difference....and OHSU's patient trials are not that large.

Will you be able to attend all the talks at ASCO? or just some of the

presentations? It will be interesting to find out what you hear. It is

really appreciated that you take all this on.

C.