“Warning” basically means, “be vigilant, consider other options, but you don’t necessarily need to do anything right now”. The next formal category is “failure” which really means action needs to be taken now, such as switch to another drug. “Failure” just means that the current treatment plan is not working, it doesn’t mean there is no hope for the patient - far, far from it.
They are big words, but as others have said the downward trend is the most important thing. The guidelines are just that - guidelines. Other factors come into play, and it certainly is true that imatinib is the most “gentle” of the TKIs (though for some people, me included, it is anything but). But when you look over a large number of people, imatinib has the fewest high grade side effects and it has the most data behind it. It is certainly the least hard for cardiac issues, and there is some (not massive) evidence to suggest imatinib can actually be cardio-protective in some ways (says my haematologist - I don’t know to what exactly she was referring to).
Some people do respond super quickly, and others are relative tortoises, but there’s no evidence to suggest that faster responses give a better long-term outcome. Getting to 0.1%, however long that takes, is the goal really. Having spoken to many eminent haematologists over the years at conferences, some will tell you that under 1% is in all likelihood not a bad place to be.
David.