FYI: Long-term Treatment With Imatinib: 5-Year Update (IRIS)

[Guest guest]

Hi all,

I'm posting below a discussion in the wake of the ASH meeting. This is

from a series about CML from ASH that I am privvy to. I'm not posting

them all because there are too many (62 pages in a pdf) but will post

some of them. I have also removed links and references for my

convenience.

Below is the first one.

~ G.

www.cmlsupport.com

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Long-term Treatment With Imatinib: 5-Year Update (IRIS)

Yang, MD, PhD:

Let us begin our discussion of the recent American Society of Hematology

(ASH) meeting with Dr. Simonsson's presentation, which provided

long-term follow-up evaluation of cytogenetic and molecular responses in

newly diagnosed chronic myeloid leukemia (CML) patients treated with

imatinib in the IRIS (International Randomized IFN vs STI571) study

(Capsule Summary).[1]

Jane Apperley, MD:

This was a highly anticipated follow-up of the IRIS study, which

included 1106 patients with newly diagnosed chronic-phase CML randomized

to receive imatinib or interferon/cytarabine. As reported 2 years ago in

the New England Journal of Medicine, the estimated rate of complete

cytogenetic response was 76.2% for patients in the imatinib arm vs 14.5%

in the interferon/cytarabine arm (P < .001) at a median follow-up of 19

months.[2] Progression to accelerated-phase or blast-crisis CML was

significantly less common in the imatinib group. In a subsequent report

later that year, Dr. and colleagues[3] indicated that many more

patients in the imatinib arm had a 3 log10 or greater reduction in

BCR-ABL transcript levels after 12 months of therapy. Furthermore,

patients achieving that level of response had an essentially negligible

risk of disease progression.

At this meeting, Dr. Simonsson and colleagues focused their attention on

the imatinib arm of the IRIS study. They found that there was an 86%

rate of complete cytogenetic remission by 54 months on imatinib, as well

as very good progression-free and overall survival, even among patients

with high-risk Sokal scores. Patients were analyzed according to the

depth of molecular response that they had previously achieved at 12

months, with a reduction in BCR-ABL transcripts of 3 log10 or greater

defined as a major molecular response. Survival without progression to

accelerated phase or blast crisis at 54 months was 100% in patients who

at 12 months had achieved a major molecular response. By comparison,

survival without progression was 95% for patients who had a cytogenetic

response that did not surpass that 3 log10 level and 89% for patients

who at 12 months had not achieved a cytogenetic response (P < .001).

These results suggest that complete cytogenetic remission is a good

prognostic indicator.

Hagop Kantarjian, MD:

The previous publication by Dr. and colleagues emphasized

progression-free survival, which was defined as maintenance of best

cytogenetic response. By contrast, the current analysis utilizes major

molecular response. Nevertheless, all patients who have a complete

cytogenetic response appear to be doing well at 5 years' follow-up.

O'Brien, MB ChB:

This presentation of longer-term data is important because it tells us

not only who is doing well but who might not do well in the long term.

We have to remember that many of these patients do not achieve the gold

standard therapeutic target of major molecular response. Although these

results are encouraging, there is still work to be done to improve the

major molecular response rate.

Jane Apperley, MD:

One additional consideration is that these data do not reveal what

proportion of patients loses these major molecular responses. If it is a

relatively small proportion, we do not have to worry. What is really

important is the fact that we have changed how we define progression.

Formerly, progression meant loss of best response. Now, progression is

defined as real progression to advanced-phase disease. We do have other

therapies that can be employed when best response is lost. For these

patients and their physicians, the critical factor is whether they

develop accelerated-phase or blast-crisis CML.

Hagop Kantarjian, MD:

You have highlighted an important point. Last year, Dr. Silver and

colleagues[4] calculated that the rate of loss of best response was

about 4% per year in the first 4 years after initiation of imatinib

therapy.However, the transformation to accelerated phase and blast

crisis is about 2% per year. Therefore, one half of the patients who

lose their best response continue to do well, whereas the other half

progress to more advanced disease. For those who lose their best

response but do not progress clinically, there is need for alternative

therapies, such as the new kinase inhibitors. For those eligible

patients, this might also mean referral to an allogeneic transplant

program.

Jane Apperley, MD:

Another important point about these results is that the rate of

development to blast phase appears to decrease with time, which

contrasts markedly with historical data.[5]