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Blood, 15 May 2002, Vol. 99, No. 10, pp. 3547-3553
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Imatinib mesylate (STI571) therapy for Philadelphia
chromosome-positive chronic myelogenous leukemia in blast
phase
Hagop M. Kantarjian,
Jorge Cortes,
Susan O'Brien,
Francis J. Giles,
Maher Albitar,
Mary Beth Rios,
Jianqin Shan,
Stefan Faderl,
Guillermo Garcia-Manero,
Deborah A. Thomas,
Debra Resta, and
Moshe Talpaz
From the Departments of Leukemia,
Hematopathology, and Bioimmunotherapy, The University of Texas MD
Anderson Cancer Center, Houston, TX, and Novartis Oncology, East
Hanover, NJ.
Molecular abnormalities caused by the hybrid Bcr-Abl gene are
causally associated with the development and progression of Philadelphia chromosome-positive (Ph+) chronic
myelogenous leukemia (CML). Imatinib mesylate (STI571), a specific
Bcr-Abl tyrosine-kinase signal-transduction inhibitor, has shown
encouraging activity in phase I and II studies of CML. Here, we
describe the use of imatinib mesylate to treat 75 patients in
blast-phase CML (median age, 53 years; 65 with nonlymphoid and 10 with
lymphoid blasts), and compare the results with those of a historical
control group treated with standard cytarabine-based therapy. Imatinib
mesylate was given as oral doses at 300 to 1000 mg per day and was the
first salvage therapy for 47 patients. The objective response rate was
52% (39 of 75 patients: 16 had complete and 3 had partial hematologic
response; 12 had hematologic improvement; 7 returned to second chronic
phase; and 1 had a complete response in extramedullary blastic
disease). Response rates were not different between nonlymphoid and
lymphoid groups. The cytogenetic response rate was 16% (12 patients: 5 complete, 3 partial [Ph+ below 35%], and 4 minor
[Ph+, 34% to 90%]). The estimated median
overall survival was 6.5 months; the estimated 1-year survival was
22%. Response to therapy (landmark analysis at 8 weeks) was associated
with survival prolongation. Compared with standard cytarabine
combinations, imatinib mesylate therapy was less toxic and produced a
higher response rate (55% versus 29%, P = .001), longer
median survival (7 versus 4 months, P = .04), and lower
4-week induction mortality (4% versus 15%, P = .07).
Imatinib mesylate is currently being tested in combination with other
drugs to improve the prognosis for blast-phase CML.
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