Today's Teleconference

[Guest guest]

Hi Everyone,

In case any of you weren't able to listen to today's teleconference

but were interested in what Dr. Cortes said, I've written a summary

in two parts. This post will look at his initial " lecture " and my

next post will have the question/answer period.

He started with a brief history of CML saying that it was the first

malignancy where a chromosomal change was found to cause a disease.

Past goals of CML therapy were simply to control blood counts but

thanks to Gleevec and other targeted therapies, our goal now is to

reach the source of the disease and allow patients to live long term.

Between the years of 1997-2007 there hasn't been much of a change in

the number of people being diagnosed with CML. Prior to 1997, 2400

patients died a year from CML and now there are less than 500

patients dying a year due to CML.

Survival has gone from 3-4 years prior to Gleevec, to now 95% of

patients are still alive after 5 years. The IRIS trial has shown us

that more than 80% of newly diagnosed patients have achieved a CCR

which has been very durable over 5 years. The longer the patients

are on Gleevec, the lower the rates of relapse are, which is very

encouraging.

He said that blood levels of Imatinib (Gleevec) can predict the level

of response a patient will have. Low concentrations of imatinib in

the blood, don't give patients as good of a response as higher

levels. He also said that serum testing of Gleevec is now widely

available.

The earlier the patient responds, the better the outcome. Patients

who are in CCR at 1 year, have the best probability of a durable

response. He mentioned that proper monitoring of disease is

essential. FISH tests can have a false positive rate of up to 10% so

that should be taken into consideration when evaluating a patients

results.

A PCR test measures the patient's molecular response. A major

molecular response (MMR) is a 3 log reduction. Each lab has a

baseline value of what a newly diagnosed patient will have in terms

of a PCR result. If for instance, the baseline is 50, then a one log

reduction would be 5, a two log reduction would be 0.5, and a three

log reduction would be 0.05.

Standard dose Imatinib has shown wonderful responses but higher dose

therapy can show faster and even deeper responses. He mentioned

though that higher dose therapy (800mg) is still considered

investigational, it's not by any means standard.

Over the long term, side effects appear to ease up in most patients.

We used to be concerned about the long term effects of taking Gleevec

but after 5 years of use, we're not so worried anymore because people

seem to be doing better and better with fewer side effects over the

long term.

Studies that have looked at heart problems have shown that Gleevec

does not cause any more heart problems than you would expect to see

in the general population.

Dasatinib (Sprycel) is effective in all stages of disease and is well

tolerated. Cytopenias (low blood counts) are a common side effect

and pleural effusions can occur in 25-30% of patients but it can be

managed. Giving 100mg once daily is showing equal responses as the

70mg twice daily dose and there's less side effects with the 100 mg

dose.

Nilotinib (Tasigna) is also showing to be very effective and well

tolerated in patients who are taking it in clinical trials. It has

shown no pleural effusions but can sometimes cause liver enzymes to

rise.

We continue to be excited about CML therapy as more hopeful drugs are

on the horizon. SKI-606 and INNO-406 are showing encouraging

responses in trials so far.

With so many drugs to chose from, there will soon be a question as to

how to select a drug to use. Side effects should be considered when

choosing a drug. Various mutations are better targeted with some

drugs over others so that's another consideration to look at.

40%-60% of patients who fail imatinib have a mutation but most of

those mutations can be managed with one of the other second or third

generation drugs. MK-0457 is showing activity against the more

serious T315I mutation, which is encouraging.

We want to eliminate the last leukemia cell, the " mother cell " so

that we can cure CML. We have had a significant amount of success in

treating CML but we still have a way to go to cure it. We are

hopeful for a cure in the " very near future " .

Clinical trials are essential for gaining knowledge so it's

important that patients continue to participate in trials if they

can.

Advances in CML have been very quick. We now have 3 generations of

inhibitors to chose from.