Imatinib mesylate (STI571) therapy for Philadelphia chromosome-positive chronic myelogenous leukemia in blast phase.

Abstract

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.

• Authors: 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, Moshe Talpaz
• Journal: Blood (Blood) Vol. 99 Issue 10 Pg. 3547-53 (May 15 2002) ISSN: 0006-4971 [Print] United States
• PMID: 11986206 (Publication Type: Clinical Trial, Comparative Study, Controlled Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Benzamides
• Enzyme Inhibitors
• Piperazines
• Pyrimidines
• Cytarabine
• Imatinib Mesylate
• Fusion Proteins, bcr-abl

Topics

• Adult
• Antineoplastic Agents (adverse effects, therapeutic use)
• Benzamides
• Blast Crisis (diagnosis, drug therapy, genetics, mortality)
• Blood Cell Count
• Cytarabine (therapeutic use)
• Cytogenetic Analysis
• Enzyme Inhibitors (adverse effects, therapeutic use)
• Follow-Up Studies
• Fusion Proteins, bcr-abl (antagonists & inhibitors)
• Humans
• Imatinib Mesylate
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (diagnosis, drug therapy, genetics, mortality)
• Middle Aged
• Philadelphia Chromosome
• Piperazines (adverse effects, therapeutic use)
• Prognosis
• Pyrimidines (adverse effects, therapeutic use)
• Survival Rate
• Treatment Outcome