To assess the response and toxicity of imatinib mesylate and low-dose cytarabine in imatinib non-responder chronic myeloid leukemia, chronic phase (CML-CP) patients: A pilot study

Abstract

17507 Background: To overcome primary imatinib mesylate (Gleevec ) resistance, we used a combination of imatinib mesylate and low dose cytarabine to treat patients of CML-CP. Methods: Between January 2005 and July 2006, 30 patients (median age 34 years, range 20 to 57 years, M:F ratio 5:1) were enrolled. 2/30 patients had primary hematological and 28/30 had primary cytogenetic resistance. 7 patients had been pretreated with interferon alpha. Treatment consisted of imatinib 400mg daily and cytarabine 10mg subcutaneous daily for 10 days every month. Median of 5 cycles (range 3–6) was administered. Patients were monitored on outpatient basis with weekly blood counts. Bone marrow cytogenetics was done 3 monthly to assess cytogenetic response (CGR). Toxicity was recorded as per NCI CTC (version 2). Primary end points were response and toxicity at the end of 6 cycles. We measured plasma imatinib levels by HPLC in 20 of these patients (J Chromatography B 2004;84:431–34) and compared the levels with 20 patients who were imatinib responders. Results: 11/30 (37%) patients obtained major CGR including complete CGR in 6/30 (20%). None of the patients with primary hematological resistance responded. Grade 3/4 hematological and non hematological toxicities were seen in 3.33% (n=1) and6.66% (n=2) patients respectively. 8/30 (27%) patients discontinued treatment due to reversible cardiac arrest (n=1), hepatitis (n=1), progression to BC/AP (n=2), grade 4 thrombocytopenia (n=1), loss of CHR (n=2), and consent withdrawl (n=1). The mean plasma imatinib levels in non responders were significantly lower, compared to imatinib responders (0.70 micro moles vs 2.34 micro moles, p=0.002). Conclusions: Present study confirms the activity of low dose cytarabine and imatinib in patients having primary cytogenetic resistance. The reasons for low plasma imatinib levels among non responders and methods to circumvent so as to achieve higher plasma levels of imatinib needs further study. No significant financial relationships to disclose.