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
risk score.
- 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
MMR.
- 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.
Dr. Francois Guilhot's Summary of IRIS Trials