High-dose (HD) imatinib in patients (pts) with previously untreated chronic myeloid leukemia (CML) in early chronic phase (CP): preliminary results of a multicenter community based trial.

6518 Background: A recent single center study suggests that using HD imatinib (800 mg/day) results in significant molecular responses for many patients. We therefore initiated a multicenter community-based single-arm phase II trial of HD imatinib in pts with early CP CML.,Pts were ≥18 years (yrs), in early CP (≤6 months from diagnosis), without prior therapy except for ≤1 month of imatinib or hydroxyurea, and with normal organ function. Pts received imatinib 400 mg twice daily and dose was adjusted for grade ≥3 toxicity; filgrastim was encouraged for pts with grade ≥2 neutropenia.,To date, 36 pts have been enrolled in 20 institutions with a median follow-up of 5 months (mos) (0.5-9 mos). The median age is 51 yrs (28-76 yrs). Nineteen patients (53%) had hemoglobin <12 g/dl and 13 (35%) had platelets >450 x10/L. According to the Sokal classification, 14 (39 %), 18 (50%), and 3(8%) were in the low, intermediate and high-risk groups, respectively. Twenty seven pts have had a molecular analysis at 3 mos from the start of therapy and 22 (81%) achieved BCR-ABL/ABL levels <0.05%, with 11 (41%) having undetectable BCR-ABL by Q-PCR. Eleven 11 pts had Q-PCR at 6 mos and 10 (91%) achieved undetectable BCR-ABL. The most common grade ≥3 non-hematologic toxicity was fatigue (n=4, 11%), rash (n=3, 8%), nausea/vomiting (n=2, 6%), and musculoskeletal pain (n=2, 6%). Twelve patients developed grade ≥3 myelosuppression, including neutropenia (n= 5,14%), thrombocytopenia (n=5,14%), and anemia (n=2, 5%). Seventeen 17 (47%) patients required treatment interruptions and 16 of those (44%) have required dose reductions. Neupogen was administered to 8 (22%) pts with 3 (8%) pts for grade ≥3 neutropenia. Most common toxicities for dose reductions were fatigue (6, 17%), nausea/vomiting (9, 25%), and rash (5, 14%).,High-dose imatinib is tolerable and effective for pts with newly diagnosed CP-CML in a multicenter setting. Compared to 400 mg daily of imatinib, pts at 800 mg daily achieve substantially higher rates of molecular response with majority having BCR-ABL/ABL ratios under 0.05% at 3 months and up to 41% having undetectable BCR-ABL on Q-PCR. [Table: see text].