Hi everyone, how often does a loss of response happen with Gleevec? I think about it a bit because there have been a few people on this site who have had it happen and have had to switch drugs. So far I have been responding well to Gleevec but just curious.
Question about loss of response
Posted 11 April 2011 - 11:40 AM
Here are some interesting facts from the IRIS trial after 5 years of data (which is now pretty out dated).
Keep in mind when reading support forums that you are more likely to encounter people who are having issues with treatment because they are the ones who tend to have more questions. People who are doing well are usually not as active so the numbers may seemed skewed when you hear about people who are having to change drugs. Also keep in mind that there is a difference between changing drugs because it stopped working vs, it is not working as well as a different drug might. When Gleevec was the only drug, if it took you three years to acheive CCyR, then you waited. Today most doctors would not wait, they would switch you to another drug to get you there faster. I wouldn't see that as loss of response as much as a poor or slower response. Also people tend to change for various side effects. Some of those are major and others are quality of life. So lots of reasons of why people may switch but at the heart of it, for many, Gleevec is very effective at its primary purpose, which is stopping progression of CML. Fortunately, today for the minority it does not work for or for those who are having a hard time with it, there are other options and that is trully wonderful.
5-Year Data on Gleevec for 1st Line Patients on 400mg Dose
* Between 2000 and 2001, 1100 newly diagnosed patients were
enrolled in the IRIS trials randomized into 2 arms, one taking
Interferon/Ara-C and the other 400mg Gleevec.
* The 5-year data has been published recently in the New England Journal
of Medicine, November 2006. The follow-up time is median 60 months.
* Gleevec shows a definite superiority over Interferon/Ara-C in terms of
responses, overall survivals and freedom from progression. This is the
reason Gleevec is now the first-line drug treatment.
* The 12 months and 60 months complete cytogenetic response (CCR) rates
were 69% and 87% respectively. Only 7% of patients on Gleevec
progressed into advanced phases in 5 years time. The overall survival
was 89% and when censored for transplant deaths and deaths unrelated to
CML, the overall survival for newly diagnosed Gleevec patients on
400mg is 95% at 5 years. Due to the excellent response rates and 5-year
survival data, Gleevec is now the first-line therapy treatment in CML
even for young patients with suitable donors.
* In the IRIS trials, 65% of patients crossed over from the Interferon arm to
join the Gleevec arm. Only 4% of Gleevec patients discontinued
treatment due to bad side-effects.
* The CHR rate at 5 years is 98%.
* At the 12 month mark of Gleevec, 69% of patients reached a CCR and
85% reached a major cytogenetic remission (MCR, 1-35%Ph+). At the
60 month mark of Gleevec, these numbers jumped to 87% CCR and 92%
MCR proving that Gleevec responses can get deeper with time.
* 96% of patients who are still receiving 400mg Gleevec from the trial had
a CCR on Gleevec.
* Responses followed the Sokal risk score with 89% of low-risk patients
reaching CCR in 5 years followed by 82% of intermediate-risk patients
and 69% of high-risk patients. The risk of disease progression to
advanced phases was also higher in high-risk patients at 17% in 5 years
followed by 8% for intermediate-risk patients and 3% for low-risk
patients. However, those patients who were high-risk by the Sokal score
but achieved a CCR, did not progress in disease. A CCR with Gleevec
gives the promise of long-term remissions for all patients whatever their
* Regarding a major molecular response (MMR) which is defined as a
1000-fold reduction of disease from diagnosis by PCR measurements, at
12 months of Gleevec, 53% achieved this. This number climbed to 80%
in 4 years. So, at 4 years of Gleevec, 80% of patients can achieve a
* At the 5 year mark, 93% of newly diagnosed patients had not progressed
in their disease. The event-free survival (no relapses in chronic phase)
was 83% at 5 years.
* The rate of progression was 1.5% in the first year, 2.8% in the second
year, 1.6% in the third year, 0.9% in the fourth year and 0.6% in the fifth
year. For patients in CCR, the rate of disease progression is 2.1% in the
first year, 0.8% in the second year, 0.3% in the third year and no
progression in the fourth year. With a CCR on Gleevec, the longer you
stay on the drug, less chances of disease progression as seen from the trial.
* Out of 350 evaluable patients, of those who had a CCR at 12 months on
Gleevec, 97% of them had not had disease progression. 93% of patients
with a MCR had no disease progression at the 5 year mark. However, of
patients with no CCR, only 81% had no disease progression in 5 years.
* Patients with a MMR to Gleevec at 18 months, there was 100%
progression-free survival. Patients with a CCR but less than a PCR 3-log
reduction, there was 98% progression-free survival. However, patients
with no CCR, had a 87% progression-free survival at 5 years.
* Gleevec with a 89% overall survival and a 17% relapse rate at 5 years
with the relapse rate falling with time has become the first-line therapy
option in CML.
* For those patients who do not respond to Gleevec or who relapse from
Gleevec, there are stronger drugs like Dasatinib, Nilotinib, Bosutinib and
many others either FDA approved or in clinical trials.
Posted 11 April 2011 - 12:26 PM
For someone who is diagnosed in chronic phase and does well on Gleevec for more than 2 years, the true loss of response rate (NOT those who switch because of side effects or plateau in response) is very low, maybe 1% - 2%. A person needs to get through the first 2 years to shake out any latent mutations that might be hiding from the beginning. After that, a loss of response is rare. A couple folks who have recently lost Gleevec response after several years appear that they may have had high risk factors to begin with, but they did not provide any information about it even though asked to do so. My assumption, from what was said, is that there were some high risk factors since at least one was diagnosed a long time ago (not originally chronic phase or whatever). So there may be one person here who has lost response after 2 years of doing well and started in chronic phase. (And there are several hundred people on here).
Posted 11 April 2011 - 12:57 PM
I was on Gleevec for 9 months before I lost response.
DX 5-2010 Started normal hydra then Gleevec for 9 months stopped working
Tasigna after 5 pills pancreatis numbers jumped up quickly
Started Sprycel 100, 8-2010 for a 3 years went down to 50 mg numbers at one point really jumped up quickly
currently on 70 mg for last 2-3 years trying to get onc to reduce dose Numbers never stabilize never MMR till 4-2017 bearly and jump up and down in and out of MMR stayed MMR for 3 months then
After 6 years on sprycel fluid on both lungs, drained still have some fluid on lungs, and currently off drug 4 months now
numbers lower then ever go figure I've never been this low of a number
last 2 tests .0686 and .0181 !!
Posted 11 April 2011 - 02:04 PM
Thanks so much, I really appreciate the information and it has made me feel so much better!!!
Posted 11 April 2011 - 04:22 PM
I was on Gleevac over three years. My response to it was excellent, I asked my onc to take me off of it because of gi issues. Most people respond to it quite well and
have minimal side effects. I had gi issues before cml. So that is probably why I didn't tolerate it as well. I am on Sprycel now and feeling much better.
Good Luck Billie
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