Na

Abbreviations: CCyR, complete cytogenetic response; MMR, major molecular response.

Abbreviations: CCyR, complete cytogenetic response; MMR, major molecular response.

group (p < 0.05), and this response was also observed earlier in HD group: at 12 months 48% in HD and 19% in SD group had achieved this response (p = 0.0001). At 24 months, 46/123 (37%) patients who can be evaluated with HD versus 9/31 (29%) of patients in SD group achieved complete molecular remission.

These data are summarized in Table 1 and compared with the results obtained with 400 mg in the IRIS trial.

These data consistently suggest that it is possible that in patients with newly diagnosed CML, the use of 800 mg imatinib as starting dose might have a better efficacy than the standard 400 mg dose. Cortes et al. further reported that treatment with high dose imatinib (800 mg) was the most significant factor associated with an increased probability of achieving a molecular response, particularly at early time points (12 months).

The Australian group conducted a phase II trial (TIDEL), in de novo CML patients, using imatinib 600 mg initially, increasing to 800 mg in case of insufficient response: (i) nonhematologic response after three months of treatment, (ii) no MCyR at six months, (iii) no CCyR atnine months, or (iv) <4 log reduction in BCR-ABL at 12 months (12). Out of the 101 patients included in the trial, 81 were assessable for the 24 months molecular response. By 12 months 89%, 45%, and 13% had achieved CCyR, >3 log, and >4 log reductions, respectively. By 24 months 92%, 65%, and 29% achieved these response levels. It was concluded that a more dose intense approach to the treatment of newly diagnosed CML patients achieved a better rate of major molecular response than lower doses, and that maintenance of dose intensity in the first six months of therapy was predictive of molecular response.

The GIMEMA (Italian) group conducted a phase II trial of imatinib 800 mg in intermediate Sokal risk in the early chronic phase of CML (13). Out the 44 patients who completed six months of the treatment, the CHR rate was 100%, and the MCyR and CCyR rates were 90% and 81%, respectively. The major molecular response rate at six months was 56%. A multinational working group (Italy, Nordic Countries, Turkey, and Israel), within the frame of Leukemia Net is exploring 400 mg versus 800 mg in high Sokal risk patients. At the present time, 80 patients have been enrolled but results are pending.

An interim analysis of a multicenter phase II trial (the RIGHT trial) has been recently presented (14).

TABLE 2 Response to High Dose Imatinib—Interim Analysis of the RIGHT Trial

TABLE 2 Response to High Dose Imatinib—Interim Analysis of the RIGHT Trial

Response

6 Mo (n = 89)

12 Mo (n = 39)

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