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 Blood, 5 March 2009, Vol. 113, No. 10, pp. 2154-2160.
Prepublished online as a Blood First Edition Paper on December 5, 2008; DOI 10.1182/blood-2008-04-154344.

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CLINICAL TRIALS AND OBSERVATIONS

Imatinib mesylate dose escalation is associated with durable responses in patients with chronic myeloid leukemia after cytogenetic failure on standard-dose imatinib therapy

Elias Jabbour1, Hagop M. Kantarjian1, Dan Jones2, Jenny Shan1, Susan O'Brien1, Neeli Reddy2, William G. Wierda1, Stefan Faderl1, Guillermo Garcia-Manero1, Srdan Verstovsek1, Mary Beth Rios1, and Jorge Cortes1

Departments of 1 Leukemia and 2 Hematopathology, University of Texas M. D. Anderson Cancer Center, Houston

We assessed the long-term efficacy of imatinib dose escalation in 84 patients with chronic myeloid leukemia in chronic phase who met the criteria of failure to standard-dose imatinib. Twenty-one patients with hematologic failure and 63 with cytogenetic failure had their imatinib dose escalated from 400 to 800 mg daily (n = 72) or from 300 to 600 mg daily (n = 12). After a median follow-up of 61 months from dose escalation, 69% remained alive. Complete cytogenetic responses were achieved in 40%; including 52% of patients with cytogenetic failure and 5% of those with hematologic failure. The estimated 2- and 3-year event-free survival and overall survival rates were 57% and 47%, and 84% and 76%, respectively. Responses were long-lasting; 88% of patients with major cytogenetic response sustained their response beyond 2 years. Treatment was well tolerated, with 76% of patients, at 12 months, continuing to receive imatinib at 100% of the intended dose. In conclusion, imatinib dose escalation can induce sustained responses in a subset of patients with cytogenetic failure and a previous cytogenetic response to standard-dose imatinib.


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