High-dose imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: high rates of rapid cytogenetic and molecular responses.

PURPOSE: Long-term clinical outcome data have established imatinib 400 mg/d as standard front-line treatment for newly diagnosed patients with chronic myeloid leukemia (CML).

PATIENTS AND METHODS: The Rationale and Insight for Gleevec High-Dose Therapy (RIGHT) trial is a multicenter study of imatinib 400 mg twice a day as initial therapy in 115 patients (70% Sokal low risk) with newly diagnosed CML in chronic phase who were observed for both molecular and cytogenetic responses for up to 18 months. Eighty-three patients (72%) completed the study, 10 patients (9%) discontinued the study because of adverse events, and six patients (5%) discontinued because of unsatisfactory therapeutic effect.

RESULTS: Polymerase chain reaction analysis demonstrated rapid kinetics of major molecular response (MMR), with 48% of patients achieving MMR by 6 months, 54% by 12 months, and 63% by 18 months. Corresponding complete molecular response rates were 39%, 44%, and 55%, respectively. Median dose-intensity was 98%. Overall, 79% of patients who received at least 90% dose-intensity achieved MMR. The most frequent adverse events included myelosuppression, rash, fatigue, and musculoskeletal symptoms.

CONCLUSION: This study suggests that imatinib 400 mg twice a day results in more rapid reduction in tumor burden than imatinib 400 mg/d with minimal added toxicity.