Five-Year Follow-up of Patients Receiving Imatinib for Chronic Myeloid Leukemia

[Guest guest]

Newly Diagnosed Myeloid Leukemia Responds to Imatinib

In a 5-year follow-up of patients with newly diagnosed CML, imatinib

was superior to interferon-{alpha} plus cytarabine.

The dramatic efficacy of imatinib (Gleevec) in chronic myeloid

leukemia (CML) patients has made it a paradigm for targeted cancer

therapies. Researchers now provide 5-year follow-up data on patients

who were treated in the phase III, industry-sponsored, IRIS study.

Eleven hundred six patients with newly diagnosed CML were randomized

to daily oral imatinib or the combination of interferon- plus

cytarabine. The primary endpoint was event-free survival; secondary

endpoints were complete hematologic, cytogenetic, and molecular

responses. Crossover was allowed for inadequate response to or

toxicity of originally assigned therapy; 65% of patients crossed

over to imatinib, whereas only 3% crossed over to interferon- plus

cytarabine. As a result, very few patients received long-term

interferon, and this report focused on the imatinib-treated

patients.

By 12 months, 96% of imatinib patients achieved complete hematologic

responses, and 69% achieved complete cytogenetic responses; these

rates were 98% and 87%, respectively, at 5 years. At 5 years, 89% of

patients were alive, and 83% had experienced no disease-related

events. The estimated annual rates of progression to accelerated

phase or blast crisis decreased over time: 1.5% in year 1, 1.8% in

year 2, 1.6% in year 3, 0.9% in year 4, and 0.6% in year 5. All

patients who achieved complete cytogenetic responses and molecular

responses (defined as >3 log reduction in BCR-ABL transcripts)

survived at 5 years, without progression to accelerated phase or

blast crisis. No difference in survival was noted between patients

who were assigned initially to imatinib and those who crossed over

to imatinib. Side effects of imatinib therapy included edema, muscle

cramps or joint pain, diarrhea, and rash. One patient developed

heart failure.

Comment: Only 7% of imatinib-treated patients progressed to

accelerated phase or blast crisis. Risk for progression decreased

over time and was <1% in years 4 and 5 of imatinib therapy; overall

survival of imatinib-treated patients was 89%. These impressive

results confirm imatinib as standard therapy for initial treatment

of CML patients. As noted by the authors, the current recommendation

is to continue therapy indefinitely, because relapses occur in some

patients when treatment is discontinued. Ongoing questions relate to

administration of higher initial doses of imatinib and integration

of next-generation kinase inhibitors (i.e., dasatinib and nilotinib)

into treatment algorithms. Safety and toxicity of long-term therapy

still require assessment, especially in view of recent reports of

cardiomyopathy and congestive heart failure in a small subset of

patients.

— E. , MD

Full report coming.

--

Zavie (age 68)

67 Shoreham Avenue

Ottawa, Canada, dxd AUG/99

INF OCT/99 to FEB/00, CHF

No meds FEB/00 to JAN/01

Gleevec since MAR/27/01 (400 mg)

CCR SEP/01. #102 in Zero Club

PCRU 5/02 at RVH (suspect)

2.8 log reduction Sep/05

3.0 log reduction Jan/06

PCRU 11/06 at The Ottawa Hospital

e-mail: zmiller@...

Tel: 613-726-1117

Fax: 309-296-0807

Cell: 613-202-0204

ID: zaviem