One of the issues CML patients struggle with is whether they are responding well to TKI drug therapy, and ask "Am I responding quickly enough?" It is normal to want a fast response, and some people do respond quickly to the TKI drugs. But it is a continual theme that people think they should be responding faster than they are, since they assume most others are doing far better. Let me put the issue into perspective, since there has been a tendency to overestimate the average speed of response to CML TKI drugs.
There is no one place to find the statistics, so I compiled them myself. And since the stats vary by study, sometimes widely, some averaging and normalizing has been done to reflect an aggregated response rates among the various studies. So these numbers will not line up with specific studies.
TKI Response Rates by Percentage (Compiled/averaged/normalized by Trey):
400 Gleevec 800 Gleevec Sprycel Tasigna
CCyR by 12 mo 66 70 77 78
CCyR by 24 mo 75 80 80 85
MMR by 12 mo 30 45 46 55
MMR by 24 mo 46 65 64 70
MMR at 7 years 83 NA NA NA
PCRU at 12 months 7 10 10 11
PCRU at 24 months 10 17 17 25
PCRU at 5 years 40 NA NA NA
CCyR is a zero BMB or FISH. MMR is a 3 log reduction by PCR. PCR Undetectable (CMR) is a zero PCR or 4.5 log reduction on some studies.
As you can see, there are quite a few patients who do not achieve CCyR by 12 months, which is why the goal for CCyR is 18 months. The MMR (3 log reduction) rate at 12 months is generally under 50%, which is why the MMR goal is about 2 years. But you can see that a significant number do not achieve MMR by 2 years. CMR/PCRU numbers at one year are generally only 10 - 20%, with the exception that Tasigna rates are higher (whether due to statistical anomalies or reality is yet to be seen), and the PCRU stats slowly rise over the years, although accurate data is not available. Long term studies show that some patients have achieved PCRU in the 7 - 10 year timeframe after a long, slow, steady response.
The positive trend lines generally continue upward as years go by. The biggest risk of drug resistance is in the first 24 months, after which the risk drops very significantly (although there are exceptions).
So it is important to have realistic near-term objectives for treatment to avoid disappointment, and to understand that an optimal response can take a long time. The stats show that over the long term, the drugs provide for a deeper level of response, and a continual decline in the probability that the drugs might quit working.
These stats should also dispel assertions that Gleevec is somehow an "inferior" drug. Response rates are somewhat lower for Gleevec up front, but Gleevec catches up fairly quickly. So if Gleevec works for a person, then there is no reason to switch unless side effects are intolerable. The main reason why patients switch from Gleevec are the side effects, not loss of response.
People respond differently to different TKI drugs, so the key is to find the one to which you respond well with tolerable side effects. The best approach for doing this is trial and error. There is no clear data to show which drug should be used from the start of treatment. But early switching in the face of any significant loss of drug response is a very good idea.
This is dedicated to all you "slow responders" who believe you are in the minority. If you look at the stats carefully, you will see that most of you are right on target. And remember, these drugs have resulted in a 95% survival rate for CML. Sometimes it is simply a matter of perspective.