CML mutations

[Guest guest]

Dear Group,

In re your discussion about mutations, I found this that you might find

interesting and may answer some of your questions.

The most common baseline mutations were G250E, E255K/V, E355G, F317L, H396R and

M351T. New mutations were found during median follow-up of 112 (6 - 350) days in

37 pts (26 without baseline mutations). New mutations most commonly included

F349V, E255K/V, E355G, G250E, M244V and T315I. Of the 37 pts, 30 had evaluations

after mutations emerged, and 15 continued to respond for median of 160 (41-351)

days. Fourteen mutations not previously reported occurred, 6 at codons with

known imatinib resistance mutations resulting in novel amino acid substitutions.

Novel mutations in multiple pts and/or multiple timepoints included E344G,

F311I, E453K, E459Q and L248L. The T315I mutation was present at baseline in 1

pt who failed to respond and emerged in 4 pts, of whom follow-up was available

for 3. Two continued to respond > 80 days after developing the mutation and one

progressed when the mutation emerged. Conclusions: AMN107 has clinical activity

in pts with Ph+CML/ALL with nonmutated and mutated Bcr-Abl. At AMN107 doses used

in this phase I study, new mutations often emerged, but were not a reliable

predictor of clinical relapse.

http://www.asco.org/ASCO/Abstracts+%26+Virtual+Meeting/Abstracts? & vmview=abst_de\

tail_view & confID=40 & abstractID=33908

I hope this helps.

Cheers,

Lottie