Goldman on Friday at ASH

[Guest guest]

Hey folks - I sent this yesterday, but it didn't seem to go though.

__________

More from the Corporate Friday Symposium. This time it¹s Goldman, one

of the Grand Old Men of CML, talking on monitoring of minimal residual

disease (MRD ­ that is, once you¹ve achieved CCR or better). Though

actually, he talked about several things not directly related to monitoring.

I¹ll just highlight a few of the intesting things I gleaned.

€ Goldman reiterated (as did just about everyone) that a 3 log reduction or

better in BCR/ABL by quantitative PCR is the current holy grail of IM

therapy. Why? because not a single patient who reached it has died in the

54 months of the trial that Goldman refers to. A 3 log or better reduction,

by the way, is called a ³major molecular response,² or MMR.

€ Goldman mentioned, as did Talpaz and others, that most patients continue

to improve their PCR results over time. Most labs can¹t detect below a 5 log

reduction, at which point Goldman estimates, we still have 10,000,000 (10^7)

cells left in our bodies ­ so reaching this is great, but it¹s by no means a

cure.

€ Goldman isn¹t a big fan of FISH testing. He believes that once we get to

CCR by conventional cytogenetics, we should be monitored exclusively by

qPCR, not by FISH.

€ On mutations: although mutations are rarely found in CML patients prior to

IM treatment, this is probably because the Ph+ that contain them are so very

much outnumbered by the Phillies that don¹t. Once IM has killed off the

non-mutated (more sensitive, that is) Phillies, the pre-existing mutated

ones expand and become detectable. This is much more likely than the

alternative: that IM somehow causes the mutations.

€ He went into the various techniques for detecting mutations, such as

direct sequencing, parasequencing, and ³allele specific PCR with clamping,²

but I didn¹t understand this bit so I¹ll spare you my garbled

interpretation!

€ What¹s the effect of mutations on survival? Patients on IM without

mutations at diagnoses have a 96% survival rate at 54 months. Patients with

mutations have an 80% survival; This drops to 32% in patients with the T315I

mutation.

€ Current recommendations for monitoring (I¹m not sure I¹ve got this just

right; others who know the current recommendations please help here):

a) Do Cyto and FISH at diagnosis, but it¹s not necessary to continue

these every three months as we¹ve done in the past. You can stop doing FISH

pretty quickly, and stop Cyto once CCR is reached.

For now, it¹s recommended that we continue with molecular monitoring

every 3 months forever

c) I definitely didn¹t catch all he said about frequency and

persistence of BMA/BMB. Continue at least till you reach CCR, but it isn¹t

necessary to continue annual BMA¹s for patients in MMR.

OK, it¹s getting late, and I know I¹ve botched at least part of this last

presentation. One problem is that these speakers are given incredibly

little time to present a whole lot of date. They do so using slides, which

they rush through and you¹re not allowed to photograph them. I don¹t know

if anyone can follow every point, but I sure can¹t!

Goodnight to all,

R