400 OR 800 mg IMATINIB FOR CML?

Blood. 2009 Mar 4. [Epub ahead of print]

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A comparison of imatinib 400 mg and 800 mg daily in the front-line treatment of patients with high risk, Philadelphia-positive, chronic myeloid leukaemia: a European LeukemiaNet study.

Baccarani M, Rosti G, Castagnetti F, Haznedaroglu I, Porkka K, Abruzzese E, Alimena G, Ehrencrona H, Hjorth-Hansen H, Kairisto V, Levato L, Martinelli G, Nagler A, Nielsen JL, Ozbek U, Palandri F, Palmieri F, Pane F, Rege-Cambrin G, Russo D, Specchia G, Testoni N, Weiss-Bjerrum O, Saglio G, Simonsson B.

Department of Hematology-Oncology "L. and A. Seragnoli", S.Orsola-Malpighi University Hospital, Bologna, Italy.

Imatinib mesylate (IM) is the standard front-line treatment of Philadelphia positive (Ph+), chronic myeloid leukemia (CML). The dose was set at 400 mg daily, but preclinical data together with results of single-arm studies, raised the suggestion that better results could be achieved with a higher dose. To investigate if the systematic use of a higher dose of IM could lead to better results, 216 Ph+ CML patients, high risk (HR) according to Sokal index, were randomized to receive IM 800 mg or 400 mg daily, front-line, for at least 1 year. The primary endpoint was the complete cytogenetic response (CCgR) rate at 1 year. The CCgR rate at 1 year was 69/108 (64%) in the high dose arm vs 63/108 (58%) in the standard dose arm (P = 0.435). No differences were detectable also in the cytogenetic response rate at 3 and 6 months, in the molecular response rate at any time point, as well as in the rate of other events, including failures and treatment discontinuation for toxicity or other reasons. 24/25 patients (94%) who could tolerate the full 800 mg dose achieved a CCgR, and only 4/17 patients (23%) who could tolerate only less than 350 mg achieved a CCgR. This study does not support the extensive use of high dose IM (800 mg daily) front-line in all CML HR patients (ClinicalTrials.gov. no. NCT00514488).