Summary of today's teleconference

[Guest guest]

Hi Everyone,

For anyone who wasn't able to listen to today's teleconference, (CML

Treatment: Measuring Your Progress with Dr. Nimer of MSKCC),

here are some notes that I took. Please note that this is the way I

heard it and may or may not be accurate as I didn't actually record

the talk.

He started out the talk with an overview of CML explaining that CML

is a myeloproliferative disease of the stem cells. It causes an

increase in white cells, platelets and sometimes can also cause the

Hgb to rise in patients. CML is easy to diagnose, they look for the

presence of the Philadelphia chromosome using either cytogenetics,

FISH or PCR. As soon as a diagnosis is made, treatment begins

(unlike some other leukemias like CLL where they can sit and watch

the disease for a while without treating it).

He mentioned that 400mg Gleevec is still the standard dose (although

600mg does appear to give more patients the 3 log reduction) but

studies are on going to compare the various doses. He said patients

can start the 400mg right away, there's no need to work up to it. He

also said that because the Gleevec kills off the bad cells quickly

and the healthy cells take a little while to grow, it's very common

to have to take a break from Gleevec in the first month or two. He

stressed that lowering the dose is not recommended, that it's far

more appropriate to take a break from the drug while the counts

recover.

He went over the data from the IRIS trial. Relapse rates in the 5th

year were less than that in the 4th year which indicates that Gleevec

works better and better over time.

He explained that the way to monitor responses is with FISH and PCR

every 3 months. As long as there is improvement, it doesn't really

matter how long it takes to get a zero FISH. Some patients who still

hadn't achieved CCR at 12 months, have gone on to get there at 18

months so the speed of getting there may not be that important, as

long as you get there.

He said that reaching PCRU is very rare and the goal of therapy is to

get a 3 log reduction which he explained is a thousand fold decrease

in bcr/abl transcripts. Although 93% of patients who get a 3 log

reduction, have managed to maintain their response over 5 years, it's

still important to monitor with PCR every 3 months so that if a

resistance develops, it will be identified early.

If a patient's response starts to slip, he suggested that it would

probably be better to switch drugs than to increase the dose of

Gleevec.

He mentioned that most mutations are responsive to Sprycel and he

also mentioned AMN-107 saying that it binds more tightly to bcr/abl

which makes it active on some mutations that Gleevec doesn't work on.

He talked about the famous cardiotoxicity report that caused such a

flap last year. He said that he hasn't seen any evidence to suggest

that Gleevec can cause heart problems or if it does, it's certainly

not a significant number of patients.

He talked about the dosing of Sprycel, mentioning that the two

standard doses are 70mg twice a day and 100mg once a day. He said

that the 70mg twice a day was causing more pleural effusions so there

is a trend towards the 100mg once a day dose which is less of a

problem.

He mentioned that very few patients are getting transplants now that

there are so many successful drug therapy options. He did suggest

however, those in accelerated or blast phase, should consider

transplant as an option because drug therapy in this group of people

doesn't seem to give durable responses.

At this point, the telephone lines were opened and people were given

a chance to ask questions.

The first question was about surgeries and should patients take any

precautions if they are planning for a surgery. He said that if

there is a high risk of infection from the surgery, then it would be

acceptable to stop taking Gleevec 1 week before the surgery to allow

the white count to rise a bit (which will help if the patient gets an

infection) but he said that for the majority of people on Gleevec,

they manage surgeries the exact same way any normal person does.

The second question was about resistance. He said that clinical

decisions shouldn't be based on one test alone. It's the trend over

time that matters. Especially with PCR's since they tend to bounce a

lot. He said that if the PCR rises significantly on one test and

then rises again on another, it should be watched closely.

Resistance can usually be confirmed in about 6 months time.

The third question was about myelodysplasia. He said that

myelodysplasia basically means " funny looking cells in the bone

marrow " . He said that there are a significant number of Gleevec

patients who appear to have " funny looking cells in their bone

marrow " but that they don't really have myelodysplastic disease and

the presence of these " funny cells " doesn't seem to have much

significance.

The fourth question was about survival expectations. He said that

after 5 years, only 5% of patients have actually died of CML, another

5% have died of unrelated causes such as car accidents so he

encouraged us all to look both ways before crossing the street

because he thinks there's a good chance that we can all live out a

normal life expectancy.

The fifth question was about using Hydrea in treatment. He said some

people still get Hydrea to start out if they have very high counts

because it can reduce the counts quickly but Hydrea shouldn't be used

long term as a means of controlling CML. Patients should either be

on Gleevec or one of the other new drugs. If a patient is resistant

to a current dose of Gleevec, there is no sense in continuing with

that dose. It should be increased or changed for another drug.

And the last question was about the various transcripts that the

PCR's detect. He said most patients have only one transcript (ie

B2A2 or B3A2 which I think he said was the most common) but a few do

have more than one. He didn't really elaborate more on that.

And that was that.

Take care,

Tracey