Efficacy of escalated imatinib combined with cytarabine in newly diagnosed patients with chronic myeloid leukemia

Wendy Deenik, JJWM Janssen, Ronnie van der Holt, GEG Verhoef, WM Smit, MJ Kersten, SMGJ Daenen, LF Verdouck, A Ferrant, AVMB Schattenberg, Pieter Sonneveld, MV Kooy, S Wittebol, R Willemze, PW Wijermans, Berna Beverloo, Bob Löwenberg, Peter Valk, GJ Ossenkoppele, Jan Cornelissen

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Abstract

Background In order to improve the molecular response rate and prevent resistance to treatment, combination therapy with different dosages of imatinib and cytarabine was studied in newly diagnosed patients with chronic myeloid leukemia in the HOVON-51 study. Design and Methods Having reported feasibility previously, we hereby report the efficacy of escalated imatinib (200 mg, 400 mg, 600 mg or 800 mg) in combination with two cycles of intravenous cytarabine (200 mg/m(2) or 1000 mg/m2 days 1 to 7) in 162 patients with chronic myeloid leukemia. Results With a median follow-up of 55 months, the 5-year cumulative incidences of complete cytogenetic response, major molecular response, and complete molecular response were 89%, 71%, and 53%, respectively. A higher Sokal risk score was inversely associated with complete cytogenetic response (hazard ratio of 0.63; 95% confidence interval, 0.50-0.79, P<0.001). A higher dose of imatinib and a higher dose of cytarabine were associated with increased complete molecular response with hazard ratios of 1.60 (95% confidence interval, 0.96-2.68, P=0.07) and 1.66 (95% confidence interval, 1.02-2.72, P=0.04), respectively. Progression-free survival and overall survival rates at 5 years were 92% and 96%, respectively. Achieving a major molecular response at 1 year was associated with complete absence of progression and a probability of achieving a complete molecular response of 89%. Conclusions The addition of intravenous cytarabine to imatinib as upfront therapy for patients with chronic myeloid leukemia is associated with a high rate of complete molecular responses (Clinicaltrials.Gov Identifier: NCT00028847).
Original languageUndefined/Unknown
Pages (from-to)914-921
Number of pages8
JournalHaematologica
Volume95
Issue number6
DOIs
Publication statusPublished - 2010

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