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Trial of higher dose imatinib with selective intensification in newly diagnosed CML patients in the chronic phase



Trial of higher dose imatinib with selective intensification in newly diagnosed CML patients in the chronic phase



Blood 102(11): 31a, November 16



The IRIS trial demonstrated that imatinib (Glivec or Gleevec) at 400 mg/day was superior to alpha interferon plus low dose cytosine arabinoside as first line therapy for de-novo chronic phase CML. To assess the tolerability and efficacy of higher doses of imatinib in this setting we are conducting a Phase II trial using imatinib at 600 mg/day increasing to 800 mg/day if specified response criteria are not met: complete haematological response (CHR) at 3 months; major cytogenetic response (MCR, <35% Ph+ cells in the bone marrow) at 6 months; complete cytogenetic response (CCR, no Ph+ cells) at 9 months, and undetectable BCR-ABL by real time Q-PCR by 12 months. Further intensification of therapy is planned with the addition of cytosine arabinoside for those patients not achieving MCR at 9 months or CCR at 12 months. Out of 103 patients enrolled to the study, 41 are currently assessable for tolerance and response at 6 months (median age 51 years, range 21-75). An average dose of 600 mg/day was achieved in 56% and 500-600 mg/day in 80%. Imatinib was given on gtoreq90% of study days in 85% of patients. Significant dose reductions (to ltoreq400 mg/day) were required at some stage in 32% of patients, due to non-hematological (9/13) or hematological toxicity (4/13). Dose reductions were reversible in 6 of the 13 patients, all of whom went back to 600 mg/day. Filgrastim was used in cases of neutropenia to maintain dose intensity; only 1 patient had a brief dose reduction for neutropenia (remote location with no access to Filgrastim). By 3 months 100% had achieved CHR. Subsequently 2 patients have lost hematologic response, 1 progressing to blast crisis after 5 months on study. We compared best response by 6 months to those achieved in the IRIS trial. In conclusion, higher dose imatinib could be achieved in most patients (average dose 556 mg/day) and was generally well tolerated. Early cytogenetic response rates are superior to responses observed in the IRIS trial using 400 mg/day but the frequency of major molecular response appears similar at 6 months. It is too early to determine whether this approach provides superior long term clinical and molecular responses.

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Accession: 035985877

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