Submitted April 29, 2008
Accepted November 23, 2008
Imatinib mesylate dose escalation is associated with durable responses in patients with chronic myeloid leukemia post cytogenetic failure on standard-dose imatinib therapy
Elias Jabbour, Hagop M Kantarjian, Dan Jones, Jenny Shan, Susan O'Brien, Neeli Reddy, William G. Wierda, Stefan Faderl, Guillermo Garcia-Manero, Srdan Verstovsek, Mary Beth Rios, and Jorge Cortes*
Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, TX, United States
Department of Hematopathology, University of Texas M. D. Anderson Cancer Center, Houston, TX, United States
* Corresponding author; email: jcortes{at}mdanderson.org.
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 EFS and OS 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 at 12 months, 76% of patients 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.
