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

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00081926.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.

Molecular response (MR) rates with high-dose imatinib. (A) Newly diagnosed patients with chronic myeloid leukemia–chronic phase receiving imatinib 800 mg/d achieved major MR (MMR) and complete molecular response (CMR) rates that increased over time. (B) The relationship between median dose-intensity and log reduction at 18 months was determined using Fisher's exact test.

Fig 2.

Comparison of molecular and cytogenetic response rates at 12 months with imatinib 800 and 400 mg/d. Molecular and cytogenetic response rates were compared between patients on the Rationale and Insight for Gleevec High-Dose Therapy (RIGHT) trial receiving imatinib 800 mg/d and historical controls from the International Randomized Study of Interferon and STI571 (IRIS) trial receiving imatinib 400 mg/d. Values from the IRIS trial (400 mg/d) reflect the estimated responses as published in the references listed; those from the RIGHT trial (800 mg/d) reflect actual response rates. In the IRIS trial, a substudy analysis of major molecular response (MMR) was performed for a group of patients (n = 124) who achieved a complete cytogenetic response (CCyR). MCyR, major cytogenetic response.