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[Sneezy12]

http://bloodjournal....bstract?papetoc

[jjg]

Thanks for posting this Frank. I tend to think the question of should we be starting with 2nd gen TKI v gleevec is an important question and these findings while from a very small % of a big data set is important data.

The conclusion in the text of the paper is " this study demonstrates that the deeper molecular responses and more selective BCR-ABL inhibition achieved with nilotinib reduce the emergence of BCR-ABL mutations and protect patients from progression to advanced disease. These results further support the use of nilotinib in patients with newly diagnosed Ph-positive CML-CP."

A lot of us are working on the premise that we start with imatinib and if that fails we move onto nilotinib or dasinib but that's not much good if on imatinib we've progressed to AP/BC. Of course the % of people for whom this applies is small and that is a very important point from this study. The abstract quotes only the number of people with emergent mutations who progressed but there were some that progressed without measured mutations. For those without access to the full paper the total number in the study was 846, evenly distributed and stratified according to Sokal score. Total number who progressed in the first 3 years were 2 or <1% (Nilotinib 300 bid), 3 or 1.1% (Nilotinib 400 bid) & 12 or 4.2% (Imatinib 400 daily). Also "At baseline, no BCR-ABL mutations were detected for any patient." and the emergence of mutations correlated with high sokal score. I think this means that mutation testing at dx would not have helped identify who should go on nilotinib rather than imatinib, but sokal score was suggestive (something old is new again).

The numbers of patients who progressed is not big enough for a full statistical analysis so we can't get too carried away with the difference in the numbers but clearly still important enough to publish in Blood. Blood is a really good solid well refereed journal. The paper which Lucky picked up on last week http://community.lls...tart=0&tstart=0 was published in Leukemia which is one of the nature journals and incredibly hard to get published in. I'm noticing a bit of trend for the data and quality of these papers to be dismissed by some in this forum, which is our loss.

One gets the feeling that there is a big push to show improved efficacy of the 2nd gen TKIs before gleevec goes off patent and of course the more research the better. I for one have such improved side effects on nilotinib and live in a country with a centralized health system so if gleevec were to be as good as the 2nd generation TKIs and much cheaper I fear being forced back onto gleevec and loosing qol.