Imatinib dose escalation in 74 failure or suboptimal response chronic myeloid leukaemia patients at 3-year follow-up

We report here on the long-term efficacy of imatinib dose escalation in 74 patients after failure to imatinib conventional dose (13 with hematologic failure and 57 patients with cytogenetic resistance) or suboptimal response (four patients for cytogenetic or molecular). Fifty-four patients received imatinib dose escalation from 400 to 600 mg and 20 patients to 800 mg. A major cytogenetic response was achieved in 41 patients (72%) who escalated imatinib dose for cytogenetic failure and in six patients (46%) with hematologic failure (P = 0.002). Complete cytogenetic response (CCyR) was achieved in 27 (37%) patients: 38% of the hematological failure patients and 42% of the cytogenetic resistant patients (P = 0.345). Cytogenetic suboptimal response patients obtained complete molecular response, whereas the patient, who escalated the dose for molecular suboptimal response at 18 months, did not obtain improvement. After 3 years of follow-up all responding patients are in sustained CCyR. The estimated 2-year PFS and OS is 87% and 85%, respectively. In conclusion, imatinib dose escalation appears to induce sustained responses in CML patients with cytogenetic resistance, in particular in those with acquired resistance. In hematological failure patients, a rapid switch to second generation TKI is instead recommended.